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TEXT-BOOK 

OF 

PHYSIOLOGICAL  AND  PATHOLOGICAL 


CHEMISTRY 


BUNGE 


FIFTH  EDITION 

BARTLEY^S 

Medical  and  Pharmaceutical 
Chemistry 

A  Text-book  for  Medical  and  Pharma- 
ceutical Students.  By  E.  H.  Baetley, 
M.  D. ,  Professor  of  Chemistry  and  Toxi- 
cology at  the  Long  Island  College  Hos- 
pital ;  Dean  and  Professor  of  Chemistry, 
Brooklyn  College  of  Pharmacy  ;  Presi- 
dent of  the  American  Society  of  Public 
Analysis;  Chief  Chemist, Board  of  Health 
of  Brooklyn,  N.  Y.  Ee vised  and  Im- 
proved. With  Illustrations,  Glossary, 
and  Complete  Index.     12mo. 

Cloth,  netp.OO;  Leather,  net  p. 50 

*  *  *  In  this  book  the  author  has  not  only 
demonstrated  his  thorough  knowledge  of  the 
subject,  but  has  written  in  a  manner  which 
clearly  shows  him  to  be  a  teacher  as  well  as  a 
writer,  by  placing  that  which  is  essential  in  such 
a  manner  as  to  at  once  arrest  the  attention  of 
the  student.  **  *  —Therapeutic  Gazette. 


P»  Blakiston's  Son  &  Co. 

PUBLISHERS 


TEXT-BOOK 

OP 

PHYSIOLOGICAL  AND  PATHOLOGICAL 

CHEMISTKY 


BY 

G.    BUNGE 

PKOFESSOE  OP  PHYSIOLOGICAL  CHEMISTRY  AT  BALE 


SECOND  ENGLISH  EDITION 


TEANSLATED   FROM  THE  FOURTH  GERMAN  EDITION 

BY' 

FLORENCE  A.   STAELING 

AND  EDITED  BY 

ERNEST   H.   STARLING,  M.D.,  F.R.S. 

PROFESSOK  OP  PHYSIOLOGY   IN  UNIVERSITY  COLLEGE,   LONDON 


PHILADELPHIA 

P.  BLAKISTON'S  SON  &  CO. 

1012  WALNUT  STREET 

1902 


Copyright,  1902,  by 
P.  Blakiston's  Son  &  Co. 


EDITOR'S  PREFACE 

Professor  Bunge's  Lectures  on  Physiological  Chemistry 
have  had  a  great  influence  on  physiological  thought  both  here 
and  abroad.  Representing  as  they  do  the  ideas  which  have 
produced  throughout  many  years  discoveries  of  fundamental 
importance  in  the  school  of  Schmiedeberg,  they  have  served 
to  spread  the  method  of  thought  of  that  school  and  to  render 
more  effective  the  work  of  men  in  other  laboratories.  Among 
these  researches,  I  might  especially  mention  those  of  Schmiede- 
berg alone  or  in  conjunction  with  his  pupils  on  the  mechanism 
of  oxidation  in  the  body,  on  the  occurrence  of  synthetic  proc- 
esses in  the  body  [e.  g.,  the  synthesis  of  hippuric  acid  in  the 
kidney,  worked  out  by  Bunge  and  Schmiedeberg),  Schroder's 
work  on  the  formation  of  urea,  Minkowski  and  J^aunyn  on 
uric  acid,  Minkowski  on  the  production  of  diabetes  by  extir- 
pation of  the  pancreas,  besides  researches  into  the  chemistry 
of  nucleins,  of  chondrin,  the  mucins  (Leathes),  and  many  other 
subjects  of  bio-chemical  interest. 

These  Lectures  have  also  the  merit  of  being  written  by  a 
man  who  was  philosopher,  mathematician  and  chemist  before 
he  was  a  physiologist,  and  who,  being  thus  in  a  position  to 
grasp  the  general  bearings  of  his  subject,  has  succeeded  in 
making  the  dry  bones  of  physiological  chemistry  interesting 
even  to  the  beginner. 

It  was  with  great  pleasure  that  I  undertook  to  edit  a  new 
.  translation  by  my  wife  of  the  latest  German  Edition,  as  I  con- 

sider  it  eminently  desirable  that  these  suggestive  Lectures  should 

be  available  for  those  students  and  medical  men  who  are  not 
X~y  familiar  with  German. 

I  would  here  especially  endorse  the  author's  recommenda- 
tion to  students  to  go  back  whenever  possible  to  the  original 


vi  editor's  preface 

papers,  copious  references  to  which  form  a  prominent  feature 
of  these  Lectures.  A  careful  study  of  a  few  of  the  classic 
researches  in  their  original  form  will  do  more  to  acquaint  a 
man  with  the  spirit  of  physiology  than  the  most  arduous 
perusal  of  text -books.  It  is  essential  to  the  healthy  develop- 
ment of  the  thinking  powers  that  they  should  have  some  work 
to  do,  and  not  be  nourished  solely  on  a  diet  of  already  digested 
material. 

Although  the  conclusions  drawn  by  the  author  are  occa- 
sionally not  those  which  would  commend  themselves  to  the 
majority  of  physiologists,  I  have  thought  it  better  to  indicate 
in  a  footnote  the  existence  of  other  opinions  rather  than  inter- 
fere in  any  way  with  the  vitalistic  mode  of  thought  which 
gives  these  Lectures  much  of  their  interest  and  individuality. 
Such  additions  are  distinguished  by  square  brackets. 

ERNEST  H.  STARLING. 

London,  March,  1902. 


PREFACE  TO  THE  FIRST  EDITION 

It  has  not  been  my  intention  to  enlarge  the  present  volume 
beyond  the  scope  of  a  text-book ;  all  disconnected  facts  and 
mere  descriptive  matter  have  therefore  been  omitted.  In 
original  research,  every  fact,  however  isolated  it  may  at  first 
seem,  may  prove  of  inestimable  value  as  a  starting-point  for 
fresh  ideas  and  inquiries.  For  this  reason,  an  exhaustive 
account  of  all  facts  is  both  valuable  and  necessary  in  a  hand- 
book. But  a  text-book  should  merely  seek  to  initiate  and 
interest  the  student,  and  to  acquaint  him  with  the  principal 
achievements  of  investigation  in  biological  sequence.  A  mass 
of  statements  and  details  would  weary  and  disgust  the  begiuner, 
and  might  deter  him  from  pursuing  the  subject  altogether. 
But  if  interest  once  be  awakened  by  a  suggestive  though  inade- 
quate treatment  of  the  subject,  the  deficiencies  may  readily  be 
supplied  by  recourse  to  the  hand-books,  or,  better  still,  by  a 
careful  perusal  of  the  original  works. 

Descriptions  of  analytic  methods  have  also  for  the  most  part 
been  avoided,  as  they  would  have  interrupted  the  main  narra- 
tive, and  as  we  already  possess  numerous  standard  works  on 
chemical  analysis  in  physiology  and  pathology,  such  as  those 
by  Hoppe-Seyler,  Leube  and  Salkowski,  Neubauer  and  Vogel. 
With  the  aid  of  such  teachers  as  these,  analysis  should  be  learnt 
and  practised  in  the  laboratory. 

On  the  other  hand,  I  have  endeavored  to  introduce  every- 
thing that  is  at  present  ripe  for  a  connected  account.  Especial 
care  has  been  bestowed  on  the  references.  The  original 
memoirs  quoted  have  been  so  chosen  that,  with  them  as  a 
basis,  the  reader  who  is  desirous  of  pursuing  the  study  of 
physiological  chemistry  will  readily  be  able  to  find  his  way 
through  its  remaining  literature,  and  will  also  have  his  atten- 


VUl  PREFACE   TO   THE   FIRST   EDITION 

tion  drawn  to  those  works  which  were  beyond  the  scope  of  my 
subject. 

If  my  lectures  succeed  in  inducing  the  study  of  the  original 
sources,  my  aim  will  have  been  attained.  Of  what  use  would 
it  be  to  the  medical  student  to  learn  up  an  exhaustive  treatise 
on  physiology?  In  a  few  years  he  would  be  no  wiser  than 
before.  In  science,  it  is  imperative  that  all  academic  teaching 
should  be  so  directed  as  to  render  the  student  capable  of  fol- 
lowing its  progress.  For  this,  a  thorough  knowledge  of  the 
exact  sciences,  physics  and  chemistry,  is  requisite ;  he  will 
then  be  in  a  position  to  read  physiological  works,  which  he 
should  be  led  to  weigh  and  discuss  critically.  No  one  will 
ever  regret  time  and  trouble  spent  in  this  way.  Later  in  life, 
he  will  find  that  he  can  always  increase  his  knowledge,  and 
that  all  medical  work  will  be  the  easier  for  it.  An  intimate 
acquaintance  with  the  exact  natural  sciences  would  shorten  and 
simplify  medical  study. 

The  object  I  have  kept  in  view  throughout  these  lectures  has 
been  to  enable  the  beginner  to  refer  at  once  to  the  most  valuable 
passages  in  the  original  works,  whenever  his  interest  has  been 
excited  in  any  question  of  physiological  chemistry. 

G.  BUNGE. 


CONTENTS 


LECTURE  I 

PAGE 

Vitalism  and  Mechanism , 1 


LECTURE   II 

The  Circulation  of  the  Chemical  Elements 13 

LECTURE  III 
Conservation  of  Energy 27 

LECTURE  IV 

The  Food  of  Man — Definition  and  Classification  op  Food- 
stuffs— The  Organic  Food-stuffs:  Proteid  and  Gelatin 41 

LECTURE  V 

The  Organic  Food-stuffs  (continued) — Carbohydrates  and  Fats 
— Significance  of  the  Three  Main  Groups  of  Organic 
Food-stuffs 60 

LECTURE   VI 

The  Organic  Food-stuffs  (conclusion) — The  Organic  Compounds 
of  Phosphorus — Cholesterin 75 

LECTURE  VII 
The  Inorganic  Food-stuffs 82 

LECTURE   VIII 
Milk  and  the  Food  of  Infants  104 

LECTURE   IX 

Subsidiary  Articles  of  Diet 115 


CONTENTS 


LECTUEE   X 

PAGE 

Saliva  and  Gastric  Juice 129 

LECTURE   XI 

The  Processes  of  Digestion  in  the  Intestine — The  Pancreatic 
Juice  and  its  Fermentative  Action — Ferments  In  General, 
— The  Action  op  the  Pancreatic  Juice  on  Carbohydrates, 
Fats,  and  Proteids  —  The  Nature  and  Significance  of 
Peptones 151 

LECTURE   XII 
Intestinal  Juice  and  Bile 172 

LECTURE   XIII 

The  Paths  of  Absorption,  and  the  Immediate  Destination  op 
the  Absorbed  Food-stuffs 187 

LECTURE   XIV 
The  Blood 200 

LECTURE   XV 
Lymph 218 

LECTURE   XVI 
The  Spleen 229 

LECTURE   XVII 

The  Gases  of  the  Blood  and  Respiration— Behavior  of 
Oxygen  in  the  Processes  of  External  and  Internal 
Respiration 237 

LECTURE   XVIII 

The  Gases  op  the  Blood  and  Respiration  (continued)  —  Be- 
havior OP  Carbonic  Acid  in  the  Processes  op  Internal 
AND  External  Respiration  —  Cutaneous  Respiration  — 
Intestinal    Gases 261 

LECTURE   XIX 

The  Nitrogenous  End-products  op  Metabolism  —  Hippuric 
Acid,  Urea,    Creatin 281 


CONTENTS  XI 

LECTUEE   XX 

PAGE 

The  Niteogenous  End-products  of  Metabolism  (continued) — Uric 
Acid  and  the  Xanthin  Group 299 

LECTURE   XXI 

The  Functions  of  the  Kidneys  and  the   Composition  of  the 

Urine 816 

LECTURE  XXII 
Metabolism  in  the  Liver — Formation  of  Glycogen 334 

LECTURE  XXIII 
The  Source  op  Muscular  Energy 348 

LECTURE  XXIV 
Formation  of  Fat  in  the  Animal  Body 358 

LECTURE  XXV 
Iron 370 

LECTURE  XXVI 
Diabetes  Mellitus 386 

LECTURE  XXVII 
Infection 408 

LECTURE  XXVIII 
Fever , 420 

LECTURE   XXIX 

The  Ductless  Glands 428 

INDICES 449 


LECTURE   I 

INTRODUCTION VITALISM    AND    MECHANISM 

By  way  of  introduction,  I  may  be  allowed  to  lay  before  my 
readers  the  views  I  hold  on  the  aims  and  prospects  of  modern 
physiological  research.  We  read  in  numberless  physiological 
papers,  and  in  the  introduction  to  almost  every  text-book  of 
physiology,  that  the  object  of  physiological  inquiry  is  to  explain 
the  phenomena  of  life  by  physical  and  chemical,  and  therefore 
ultimately  by  mechanical  laws.  A  physiologist  of  the  present 
day  would  be  regarded  as  lacking  both  in  intelligence  and 
industry,  were  he  to  take  refuge,  as  at  one  time  the  '  vitalists ' 
did,  in  the  assumption  of  a  special  '  vital  force '  as  a  means  of 
explaining  biological  problems.  I  can  only  accept  this  view  in 
a  modified  form,  and  with  the  understanding  that  no  explana- 
tion is  offered  by  a  mere  term.  I  regard  '  vital  force '  as  a 
convenient  resting-place  where,  to  quote  Kant,  "  reason  can 
repose  on  the  pillow  of  obscure  qualities." 

But  I  cannot  assent  to  the  doctrine  which  some  opponents 
of  vitalism  maintain,  and  which  would  have  us  believe  that 
in  living  beings  there  are  no  other  factors  at  work  than  simply 
the  forces  and  matter  of  inorganic  nature.  We  certainly 
cannot  recognize  more  than  these  forces,  owing  to  the  limita- 
tion of  our  powers,  since  in  the  observation  of  both  organic 
and  inorganic  nature  we  always  make  use  of  the  same  organs 
of  sense,  which  react  only  to  certain  forms  of  motion.  A  form 
of  motion  transmitted  to  the  brain  by  the  fibers  of  the  oj)tic 
nerves  arouses  in  us  the  consciousness  of  light  and  color  ;  the 
consciousness  of  sound  is  due  to  another  form  of  motion  trans- 
mitted by  the  auditory  nerve  ;  all  our  sensations  of  taste  and 
smell,  of  temperature  and  touch,  are  due  to  forms  of  motion. 
At  least  this  is  what  physics  teaches  us  ;  these  appear  to  be  at 
present  the  most  fruitful  hypotheses.  It  would  indeed  be  a 
lack  of  intelligence  to  expect,  with  the  same  senses,  to  make 
discoveries  in  living  nature  of  a  difiPerent  order  to  those  revealed 
to  us  in  inorganic  nature. 

But  for  the  study  of  organic  nature  we  possess  one  addi- 
tional sense,  our  'internal  sense':    the  power  of  studymg  and 

1  1 


Z  LECTURE    I 

observing  the  conditions  and  processes  of  our  own  conscious- 
ness. To  hold  that  this  also  is  a  variety  of  motion  is,  in  my 
opinion,  an  untenable  doctrine.  The  simple  fact  that  many 
conditions  of  consciousness  have  no  relation  to  space  is  opposed 
to  such  a  view.  Only  what  consciousness  has  acquired  by 
certain  senses,  sight,  touch,  muscular  sense,^  is  related  to  space. 
All  other  sensations,  emotions,  passions,  and  an  unlimited 
number  of  ideas  have  no  relation  to  space,  but  only  to  time. 
We  cannot  here,  then,  speak  of  a  mechanism.  It  might  be 
suggested  that  this  is  only  an  apparent  difference — that  in 
reality  these  also  have  spatial  qualities.  But  such  an  opinion 
cannot  be  sustained.  We  suppose  that  objects  which  we  per- 
ceive with  our  senses  have  spatial  qualities  simply  on  the 
ground  that,  so  far  as  we  can  observe  them  by  means  of  our 
senses,  touch  and  sight,  they  seem  to  possess  them.  But  for 
the  whole  world  of  our  internal  sense,  we  have  not  even  this 
apparent  reason,  so  that  we  cannot  admit  that  there  is  any 
ground  for  such  a  supposition. 

Therefore  the  deepest  insight  we  can  gain  into  the  most 
essential  part  of  our  nature  shows  us  something  quite  different, 
shows  us  things  which  are  without  spatial  qualities,  and  proc- 
esses which  can  have  nothing  to  do  with  mechanism. 

The  opponents  of  vitalism,  those  who  support  the  mechanical 
explanation  of  life,  usually  seek  to  justify  their  views  by  saying 
that  the  further  physiology  advances,  the  more  does  it  become 
possible  to  explain,  on  physical  and  chemical  grounds,  phenom- 
ena which  have  hitherto  been  regarded  as  associated  with  a 
special  vital  force ;  that  it  is  only  a  question  of  time ;  that  it 
will  finally  be  shown  that  the  whole  process  of  life  is  only  a 
more  complicated  form  of  motion  regulated  solely  by  the  laws 
which  govern  inorganic  nature. 

But  to  me  the  history  of  physiology  teaches  the  exact 
opposite.  I  think  the  more  thoroughly  and  conscientiously 
we  endeavor  to  study  biological  problems,  the  more  are  we 
convinced  that  even  those  processes  which  we  have  already 
regarded  as  explicable  by  chemical  and  physical  laws,  are  in 
reality  infinitely  more  complex,  and  at  present  defy  any  attempt 
at  a  mechanical  explanation. 

1  The  ideas  of  space,  which  are  connected  with  the  sensations  of  sight  and 
touch,  are  possibly  only  brought  about  by  the  complex  muscular  apparatus,  which 
plays  a  part  in  all  the  functions  of  the  organs  of  sight  and  touch.  This  is  also 
true  of  the  so-called  '  common  sensations.'  The  ideas  of  space  may  be  due  to 
the  sensory  fibers  of  the  muscular  nerves  only.  This  view  was  first  upheld  by 
Steinbach  ("  Beiträge  zur  Physiologie  der  Sinne,"  Nürnberg,  1811),  and  contested 
by  Joh.  Müller  ("Zur  vergleichenden  Physiologie  des  Gesichtssinnes,"  p.  52: 
Leipzig,  1826),  but,  in  my  opinion,  on  unsatisfactory  grounds.  Joh.  Müller  was 
a  supporter  of  Kant's  doctrine  of  space,  which  likewise  appears  to  me  untenable. 


INTRODUCTION VITALISM    AND    MECHANISM  Ö 

Thus  we-  have  been  satisfied  to  account  for  the  absorption 
of  food  from  the  alimentary  canal  by  the  laws  of  diffusion  and 
osmosis.  But  we  now  know  that,  as  regards  osmosis,  the  wall 
of  the  intestine  does  not  behave  like  a  dead  membrane.  We 
know  that  the  intestinal  wall  is  covered  with  epithelium,  and 
that  every  epithelial  cell  is  in  itself  an  organism,  a  living  being 
with  the  most  complex  functions ;  we  know  that  it  takes  up 
food  by  the  active  contraction  of  its  protoplasm  in  the  same 
way  as  observed  in  independent  naked  animal  cells,  such  as 
amebae  and  rhizopods.  Observations  on  the  intestinal  epithe- 
lium of  cold-blooded  animals  have  made  it  obvious  that  the 
cells  grasp  the  particles  of  fat  contained  in  the  food  by  means 
of  protoplasmic  processes  which  they  send  out ;  that  they  in- 
corporate the  fat-globules  with  the  protoplasm  of  the  cell, 
which  finally  passes  them  on  to  the  commencement  of  the 
lacteals.^  As  long  as  this  active  intervention  of  cells  was  un- 
known, it  was  impossible  to  understand  the  remarkable  fact 
that,  although  the  minute  drops  of  fat  were  able  to  pass 
through  the  intestinal  wall,  yet  finely  divided  pigments,  in- 
tentionally introduced  into  the  intestine,  remained  quite  un- 
absorbed.  At  the  present  time  we  know  that  all  unicellular 
organisms  possess  the  power  of  selecting  their  food,  of  taking 
up  the  useful  and  rejecting  the  useless  substances.  In  this 
connection,  I  may  relate  an  interesting  observation  made  by 
Cienkowski  ^  on  an  ameba,  called  the  Vampyrella. 

The  Vampyrella  Spirogyroe  is  a  minute  red-tinged  cell 
devoid  of  any  special  limiting  membrane,  and  apparently 
quite  structureless.  Cienkowski  could  find  no  nucleus  in  the 
cell,  and  the  small  granules  observed  in  the  protoplasm  were 
probably  only  residues  of  nutrient  matter.  This  minute  mass 
of  protoplasm  will  take  but  one  form  of  food,  a  particular 
variety  of  algae,  the  Spirogyra.  It  can  be  observed  to  send 
out  pseudopodia  and  to  creep  along  the  Confervse  until  it 
meets  with  a  Spirogyra ;  then  it  affixes  itself  to  the  cellulose 
coat  enclosing  one  of  the  cells  of  the  latter,  dissolves  the  coat 
at  the  point  of  contact,  sucks  in  the  contents  of  the  cell,  and 
travels  to  the  next  to  repeat  the  process.  Cienkowski  never 
saw  the  Vampyrella  attack  any  other  class  of  algse,  or  even 

^  R.  Wiedersheim,  has  given  an  account  of  the  older  literature,  together  with 
his  own  investigations  on  this  subject  in  the  "  Festschrift  der  56.  Versammlung- 
deutscher Naturforscher  und  Aerzte,  gewidmet  von  der  naturforschenden 
Gesellschaft  zu  Freiburg  i.  B."  Freiburg  und  Tübingen :  1883 ;  and  G.  H. 
Theodor  Eimer,  Biolog.  Centralbl.,  vol.  iv.  p.  580:  1884;  and  Heidenhain, 
Pflüger's  Arch.,  vol.  xliii.,  Suppl.  :  1888. 

^L.  Cienkowski,  "Beiträge  zurKenntniss  der  Monaden,"  Arch.  f.  niikrosk, 
Anatomie,  vol.  i.  p.  203  :  1865. 


4  LECTURE   I 

take  up  any  other  substance ;  Vaucherise,  CEdogonise,  purposely 
placed  before  it,  were  always  rejected. 

Another  monad,  the  Colpodella  jiugnax,  was  observed  by 
Cienkowski  to  feed  exclusively  on  Chlamydomonas  :  "  it  punc- 
tures, as  it  were,  the  latter,  absorbs  the  escaping  chlorophyl, 
and  departs."  "  The  behavior  of  these  monads,"  says  Cien- 
kowski, "  in  their  search  after  food  and  in  their  method  of 
absorbing  it,  is  so  remarkable,  that  one  can  hardly  avoid  the 
conclusion  that  the  acts  are  those  of  conscious  beings." 

If  this  power  of  selecting  food  is  possessed  by  the  structure- 
less mass  of  protoplasm,  why  should  it  not  also  be  a  function  of 
the  epithelium  of  our  intestine  ?  Just  as  the  Vampyrella  picks 
out  the  Spirogyra  from  amongst  all  other  algae,  so  do  the  epi- 
thelial cells  of  our  intestines  select  the  fat-drops  and  reject  the 
pigment-granules.  We  know  that  the  epithelium  of  the  in- 
testine prevents  the  absorption  of  a  whole  series  of  poisons,  in 
sjDite  of  the  fact  that  the  latter  are  easily  soluble  in  the  gastric 
and  intestinal  juices.  Indeed,  we  know  that  these  poisons  when 
injected  into  the  blood,  are  excreted  by  the  intestine. 

It  was  likewise  once  thought  that  the  activit}^  of  glands 
and  the  processes  of  secretion  were  in  the  main  explicable  by 
osmosis.  But  we  now  know  that  here  too  the  epithelial  cells 
play  an  active  part.  Here  again  we  find  the  same  mysterious 
power  of  selection,  of  picking  out  certain  constituents  of  the 
blood,  of  altering  them  by  processes  of  synthesis  and  decom- 
position, of  sending  some  into  the  ducts  of  the  glands,  and 
others  back  mto  the  lymph  and  blood.  The  epithelial  cells  of 
the  mammary  gland  collect  all  the  inorganic  salts  from  the 
blood — which  has  a  totally  diiferent  constitution — in  the  exact 
proportion  required  by  the  infant,  that  its  growth  and  devel- 
opment may  assimilate  it  to  its  parents.  These  phenomena 
cannot  at  present  be  explained  by  the  laws  of  diffusion  and 
osmosis. 

All  the  cells  of  our  tissues  possess  the  same  wonderful 
powers  as  the  epithelial  cells  of  the  alimentary  canal  and  of 
glands.  Consider  the  mode  of  development  of  our  organism  : 
all  tissue  elements  are  produced  from  a  single  ovum,  and  in 
proportion  as  the  cells  increase  by  segmentation,  they  become 
differentiated  on  the  principle  of  the  division  of  labor  ;  every 
cell  acquires  the  faculty  of  rejecting  some  substances,  of  attract- 
ing others  and  storing  them  up,  thereby  attaining  the  composi- 
tion necessary  for  the  due  fulfilment  of  the  functions  it  has  to 
perform.  But  it  is  hopeless  to  offer  a  chemical  explanation  of 
this  process. 

Just   as    little  has  it   been  possible,  in  other  branches  of 


i      INTEODUCTIOX VITALISM    AND    MECHANISM  5 

physiology  besides  that  of  uutrition,  to  refer  any  single  vital 
process  to  the  laws  of  chemistry  and  physics. 

We  have  sought  to  explain  the  functions  of  nerve  and 
muscle  by  the  laws  of  electricity,  and  must  now  admit  that 
electrical  processes  have  been  demonstrated  with  certainty  to 
occur  in  the  living  organism  only  in  a  few  fishes ;  or  even  if  we 
grant  that  electrical  currents  have  been  decisively  proved  to 
exist  in  muscles  and  nerves,  we  are  bound  to  confess  that  the 
explanation  of  the  functions  of  nerve  and  muscle  is  but 
slightly  advanced  thereby. 

It  may  be  suggested  that  the  physiology  of  the  special 
senses  offers  a  field  for  precise  physical  explanations.  It  is 
true  that  the  eye  is  a  physical  apparatus,  an  optical  apparatus, 
a  camera  obscura.  The  image  on  the  retina  is  formed  by 
the  same  unchanging  laws  of  refraction  as  the  image  on  the 
sensitive  plate  of  a  photographer.  But  it  is  not  a  vital  process. 
The  eye  is  absolutely  passive  in  the  matter.  The  image  on 
the  retina  is  formed  in  an  eye  separated  from  the  body  and 
dead.  The  development  of  the  eye  is  a  vital  process.  How  is 
this  complex  optical  apparatus  formed?  Why  do  the  cells 
arrange  themselves  so  as  to  produce  this  wonderful  structure  ? 
This  is  the  great  problem  towards  the  solution  of  which 
nothing  has  yet  been  done.  The  succession  of  events  in  de- 
velopment may  indeed  be  observed  and  described,  but  of  the 
wherefore,  the  causal  connection,  we  know  absolutely  nothing. 
The  process  of  accommodation  is  a  vital  process.  Here  again 
we  have  to  deal  with  the  old  unsolved  question  of  muscle  and 
nerve.  The  same  is  true  of  the  other  organs  of  sense.  We 
can  explain  physically  nothing  but  those  processes  in  which  the 
organ  is  quite  passively  set  in  vibration  by  external  impulses. 

The  same  is  true  of  all  other  branches  of  physiology.  We 
have  endeavored  to  explain  the  phenomena  of  the  circulation 
of  the  blood  on  a  physical  basis.  The  blood  is  certainly  subject 
to  the  laws  of  hydrostatics  and  hydrodynamics,  but  it  is  per- 
fectly passive  as  regards  circulation.  No  one  has  hitherto  been 
able  to  explain  the  active  functions  of  the  heart  and  muscular 
wall  by  a  reference  to  physical  laws.  An  attempt  has  been 
made  to  explain  the  gaseous  interchange  which  occurs  in  the 
lungs,  by  the  laws  of  aerodynamics,  of  absorption  and  diffusion, 
and  it  is  possible  that  the  attempt  may  be  successful.  Here 
again,  however,  we  are  not  dealing  with  a  vital  phenom- 
enon. The  respiratory  bellows  being  set  into  motion,  the 
gases  move  in  and  out  according  to  the  unchangeable  laws 
of  dynamics,  but  we  have  to  inquire  how  the  respiratory  bellows 
are  formed  and  maintained,  and  how  they  are  able  to  carry  out 


b  LECTURE    I 

their   movements.     Throughout  the  whole   process   the   gases 
play  only  a  passive  part. 

I  maintain  that  all  the  processes  of  our  organism  capable  of 
explanation  on  mechanical  principles  are  as  little  to  be  regarded 
as  vital  phenomena  as  the  rustling  of  leaves  on  a  tree,  or  as  the 
movement  of  the  pollen  when  blown  from  stamen  to  pistil. 
Here  we  have  a  form  of  motion  essential  to  the  phenomenon 
of  life,  and  yet  no  one  would  consider  it  a  vital  act,  simply 
because  the  pollen  is  quite  passive  under  it.  It  does  not  in  the 
least  alter  the  main  point  at  issue,  whether  the  source  of  motion 
is  formed  by  the  kinetic  energy  of  the  wind,  or  by  the  sunlight 
which  induces  the  wind,  or  by  the  latent  chemical  energy  into 
which  the  sunlight  has  been  converted. 

The  mystery  of  life  lies  hidden — in  activity.^  But  the  con- 
ception of  activity  has  come  to  us,  not  as  the  result  of  sensory 
perceptions,  but  from  the  study  of  our  own  internal  conscious- 
ness. We  transfer  to  the  objects  of  our  sensory  perception, 
to  the  organs,  to  the  tissue-elements  and  to  every  minute  cell, 
something  which  we  have  acquired  from  our  own  consciousness. 
This  is  the  first  attempt  towards  a  psychological  explanation  of 
all  vital  phenomena. 

If,  as  it  thus  appears,  it  is  impossible  to  explain  vital 
phenomena  by  the  help  of  physics  and  chemistry  alone,  we 
must  inquire  what  the  other  auxiliaries  to  the  science  of  physi- 
ology— the  morphological  sciences,  anatomy  and  histology — 
can  do  for  us. 

I  hold  that  there  is  at  present  but  little  likelihood  of  attain- 
ing our  aim  by  their  means.  For  when  we  have,  with  the  aid 
of  scalpel  and  microscope,  carried  our  anatomical  analysis  to  its 
utmost  limit,  to  the  simple  cell,  we  still  have  the  great  prob- 
lem to  face.  The  most  simple  cell — a  formless,  structureless, 
minute  mass  of  protoplasm — exhibits  all  the  essential  processes 
of  life,  as  nutrition,  growth,  reproduction,  movement,  reaction 
to  stimulation  ;  it  even  displays  functions  which  act  at  least  as 
a  substitute  for  the  psychical  powers  of  higher  organisms. 
You  will  remember  that  it  is  so  in  the  case  of  the  Vampyrella, 
and  I  should  like  to  call  your  attention  to  the  still  more  re- 
markable observations  which  Engelmann  has  made  on  the 
Arcellse.^ 

^  Activity  and  life  are  perhaps  two  words  for  the  same  idea,  or  rather  two 
words  to  which  no  definite  idea  is  attached.  And  yet  these  vague  terms  are  all 
that  we  have  at  our  command.  Here  we  approach  the  most  difiicult  problems, 
which  have  foiled  all  attempts  at  solution. 

2  Th.  W.  Engelmann,  "  Beiträge  zur  Physiologie  des  Protoplasmas,"  Pflüger's 
Arch.,  vol.  ii.  p.  307 :  1869.  Compare  also  vol.  xxv.  p.  288,  Note  I.  1881 ;  vol. 
xxvi.  p.  544,  1881;  vol.  xxx.  pp.  96,  97,  1883;  and  Max  Verworn,  Pflüger's 
Arch.,  vol.  liii.  p.  140, 1893. 


INTRODUCTION VITALISM    AND    MECHANISM  7 

The  Arcellse  are  also  unicellular  organisms,  but  they  are  more 
complex  than  the  Vampyrella,  because  they  have  a  nucleus  and 
a  shell.  This  shell  has  a  convex-concave  form.  In  the  middle 
of  the  concave  side  of  the  shell  is  an  opening  from  which  the 
pseudopodia  project,  appearing  as  clear  protuberances  at  the 
edge  of  the  shell.  If  a  drop  of  water  containing  Arcellse  be 
placed  under  the  microscope,  it  often  occurs  that  one  of  them 
falls  on  its  back  as  it  were,  i.  e.,  with  the  convex  side  downwards 
on  the  slide,  so  that  the  pseudopodia  which  appear  at  the  edge 
of  the  shell  cannot  reach  any  support.  It  is  then  observed 
that,  near  the  edge  on  one  side,  minute  bubbles  of  gas  make 
their  appearance  in  the  protoplasm ;  this  side  consequently 
becomes  lighter  and  floats  up,  so  that  the  animal  now  rests 
upon  the  opposite  sharp  edge.  It  is  now  able,  by  means  of  its 
pseudopodia,  to  grasp  the  slide  and  thus  completely  to  turn 
over,  so  that  all  the  pseudopodia  are  downwards.  The  gas- 
bubbles  now  disappear,  and  the  animal  crawls  away.  If  a  little 
water  containing  Arcellse  be  dropped  on  the  under  side  of  a 
cover-glass,  and  the  latter  be  placed  in  a  small  gas-chamber,  it 
is  observed  that  the  animalcules  at  first  sink  to  the  bottom  of 
the  drops.  If  they  find  nothing  to  lay  hold  of,  large  bubbles 
of  gas  are  developed  in  the  protoplasm,  and  as  they  are  thus 
rendered  specifically  lighter  than  the  water,  they  rise  in  the 
drops.  If  they  reach  the  surface  of  the  glass  in  such  a  position 
that  they  cannot  attach  themselves  to  it  by  their  pseudopodia, 
the  gas-bubbles  are  diminished  on  one  side  or  increased  on  the 
other  (sometimes  simultaneously  on  both),  until  a  tilting  takes 
place  and  the  edge  of  the  shell  comes  in  contact  with  the  glass, 
and  they  are  thus  enabled  to  turn  over.  When  once  this  is 
accomplished,  the  bubbles  again  disappear,  and  the  animal  can 
now  crawl  freely  about  the  glass.  If  the  Arcellse  are  carefully 
detached  by  means  of  a  needle,  they  at  first  fall  to  the  bottom, 
and  then  go  through  the  same  proceedings  anew.  Whatever 
attempt  may  be  made  to  put  them  into  an  inconvenient  position, 
they  are  always  able,  by  the  development  of  gas-bubbles  of 
appropriate  size  and  at  the  proper  spot,  to  right  themselves,  so 
that  they  acquire  a  position  favorable  to  locomotion  ;  and  the 
attainment  of  this  object  is  always  followed  by  the  disappear- 
ance of  the  bubbles.  "  It  cannot  be  denied,"  says  Engelmann, 
"that  these  facts  point  to  psychical  processes  in  the  proto- 
plasm." 

Whether  this  view  of  Engelmann's  is  justified  or  not,  I  do 
not  venture  to  decide.  I  will  even  unreservedly  admit  that 
these  remarkable  phenomena  may  find  a  mechanical  expla- 
nation.    I  have  brought  these  facts  to  your  notice  merely  in 


8  LECTURE    I 

order  to  show  you  what  complex  manifestations  of  life  we  meet 
with,  in  cases  where  microscopical  investigation  has  already 
reached  its  limit,  and  how  little  it  has  at  present  been  possi- 
ble to  explain  any  single  vital  process  on  purely  mechanical 
grounds.  For  the  cells  of  which  our  body  is  composed  exhibit 
processes  which  are  at  least  as  complicated  as  those  of  the 
simple  organisms.  Every  one  of  the  innumerable  microscopic 
cells  of  which  our  body  is  made  up  is  a  microcosm,  a  world  in 
itself. 

It  is  a  well-known  fact  that  through  one  single  spermato- 
zoon, through  this  minute  cell,  five  hundred  millions  of  which 
would  hardly  occupy  one  cubic  millimeter,  all  the  physical  and 
intellectual  peculiarities  may  be  transmitted  from  father  to  son, 
or,  even  skipping  the  son,  may  again,  by  the  agency  of  one 
single  minute  cell,  reappear  in  the  grandson.  If  this  is  really 
a  mechanical  process,  how  wonderful  must  be  the  molecular 
structure,  how  complicated  the  interchange  of  forces,  how  in- 
tricate the  forms  of  motion,  in  this  small  cell  which  shall  direct 
all  subsequent  forms  of  motion,  and  the  mode  of  development 
for  generations  !  And  how  shall  this  minute  structure  transmit 
mental  qualities  ?  Here  we  are  utterly  abandoned  by  physics, 
chemistry,  and  anatomy. 

Many  centuries  may  pass  over  the  human  race,  many  a 
thinker's  brow  be  furrowed,  and  many  a  giant  worker  be  worn 
out,  ere  even  the  first  step  be  taken  towards  the  solution  of  this 
problem.  And  yet  it  is  quite  conceivable  that  a  sudden  flash 
of  light  may  illumine  the  darkness.  You  would  misunder- 
stand me,  were  you  to  take  my  exposition  as  a  confession  that  I 
imagine  that  science  has  impassable  boundaries.  Science  will 
continue  to  ask  and  to  answer  even  bolder  questions.  Nothing 
can  stop  its  victorious  career,  not  even  the  limitations  of  our 
intellect.  This  too  is  capable  of  being  made  more  perfect. 
There  is  no  rational  ground  for  thinking  that  the  continuous 
progression,  development,  and  ennoblement  of  type  which 
has  been  going  on  for  centuries  on  this  planet,  should  come 
to  an  end  with  us.  There  was  a  time  when  the  only  living 
creatures  were  the  infusoria  floating  in  the  primeval  sea,  and 
the  time  may  come  when  a  race  may  dominate  the  globe  as 
superior  to  ourselves  in  intellectual  faculties  as  we  are  to  the 
infusoria. 

We  must  therefore  unreservedly  admit  that  the  stupendous 
difficulties  which  at  present  beset  physiological  investiga- 
tions may  finally  be  overcome.  But  for  the  moment  it 
is  not  apparent  how  any  further  progress  of  importance  can 
be  made  with    the    help  of   chemistry,  physics,  and  anatomy 


IXTRODUCTIOX VITALISM    AXD    MECHANISM  9 

only.  The  smallest  cell  exhibits  all  the  mysteries  of  life, 
and  our  present  methods  of  its  investigation  have  reached 
their  limit. 

But  we  may  improve  our  methods,  we  may  acquire  micro- 
scopes of  still  higher  power  than  those  we  now  possess.  The 
cell  which  at  present  appears  to  be  without  structure,  may 
show  a  nucleus  when  treated  with  some  new  stain.  And  the 
nucleus  itself  displays  a  structure  so  complex  that  it  will  soon 
require  the  entire  attention  of  numerous  observers  for  its 
adequate  investigation  and  description.  But  unfortimately  a 
complex  structure  is  no  explanation ;  it  only  offers  a  new  prob- 
lem as  to  its  mode  of  origin.  And  moreover  how  little  does 
our  knowledge  of  this  structure  help  us  to  understand  even 
the  simple  processes  observable  in  the  A'^ampyrell  and  the 
Arcella ! 

For  all  this,  physiological  inquiry  must  commence  with  the 
study  of  the  most  complicated  organism,  that  of  man.  Apart 
from  the  requirements  of  practical  medicine,  this  is  justified  by 
the  following  reason,  which  leads  us  back  to  the  starting-point 
of  our  remarks  :  that  in  researches  upon  the  human  organism 
we  are  not  limited  to  our  physical  senses,  but  also  possess  the 
advantage  afforded  by  the  '  internal  sense,'  or  self-observation. 
In  fact  we  may  in  this  way  approach  the  problems  of  physiology 
from  two  sides,  just  as  in  mining  or  tunnelling  the  workmen 
excavate  from  two  directions,  until  those  on  one  side  hear 
through  the  intervening  stone  the  strokes  of  the  hammers  of 
those  on  the  other. 

To  the  clear  recognition  of  the  value  of  this  method,  which 
enables  us  to  attack  the  problem  from  two  sides,  is  due 
Johannes  Müller's  great  discovery  of  the  law  of  the  "  specific 
energy  of  the  senses,"  which  is  without  doubt  the  greatest 
achievement  both  of  physiology  and  psychology,  and  the  exact 
basis  of  all  idealistic  philosophy.^  I  mean  the  simple  law,  that 
the  same  stimulus,  the  same  external  phenomenon,  acting  on 
different  organs  of  sense,  always  produces  different  sensations  ; 
and  that  different  stimuli  acting  on  the  same  organ  of  sense 
always  produce  the  same  sensation.  The  phenomena  of  the 
outer  world  therefore  have  nothing  in  common  with  the  sen- 
sation and  ideas  they  call  forth  in  us,  and  the  states  and  proc- 
esses of  our  own  consciousness  are  alone  immediately  subject 
to  our  observation  and  recognition. 

This  simple  truth  is  the  greatest  and  deepest  ever  thought 

^  In  the  disputation  for  liis  doctorate,  Joh.  Müller  maintained  the  thesis : 
"Psychologus  nemo  nisi  Physiologus."  The  time  will  come  when  the  converse 
thesis  :     "  Physiologus  nemo  nisi  Psychologus  "  will  stand  in  no  need  of  defence. 


10  LEcrruRE  I 

out  by  the  human  intellect,  and  leads  us  at  once  to  a  complete 
understanding  of  what  constitutes  the  essence  of  vitalism. 
The  essence  of  vitalism  does  not  lie  in  being  content  with  a 
term  and  abandoning  reflection,  but  in  adopting  the  only  right 
path  of  obtaining  knowledge  which  is  possible,  in  starting  from 
what  we  know,  the  internal  world,  to  explain  what  we  do  not 
know,  the  external  world. 

The  opposite  and  erroneous  view  is  adopted  by  mechanism, 
which  is  no  other  than  materialism ;  it  starts  from  the  un- 
known, the  external  world,  to  explain  the  known,  the  internal 
world. 

The  physiologist  is  continually  being  driven  back  to 
materialism  by  the  fact  that  in  psychology  no  attempt  has 
yet  been  made  to  attain  an  exactness  to  which  the  studies  of 
physics  and  chemistry  have  accustomed  us.  It  cannot  be 
denied  that,  although  nothing  is  so  immediately  under  observa- 
tion as  the  conditions  and  processes  of  our  own  consciousness, 
it  is  precisely  on  this  subject  that  our  knowledge  is  most 
vague  and  uncertain.  There  are  numerous  reasons  for  this. 
The  object  is  more  complicated,  the  qualities  are  much 
more  numerous,  than  in  the  outer  world;  moreover,  the 
states  and  processes  in  our  consciousness  are  ever  undergoing 
rapid  variations ;  and,  finally,  we  possess  at  present  no 
means  of  quantitatively  estimating  the  objects  of  our  internal 
sense. 

So  long  as  psychology  remains  in  this  condition,  we  cannot 
arrive  at  satisfactory  explanations  of  vital  processes.  In  most 
branches  of  physiology,  there  is  nothing  to  be  done  but  to 
proceed  along  the  same  mechanical  lines.  This  method  is 
undoubtedly  valuable  ;  we  must  endeavor  to  advance  as  far 
as  possible  by  the  sole  help  of  chemistry  and  physics.  What 
these  sciences  fail  to  achieve  will  stand  out  more  prominently, 
and  thus  the  mechanical  theories  of  the  present  will  assuredly 
carry  us  eventually  to  the  vitalism  of  the  future. 

The  views  put  forward  here  have  been  attacked  from  various 
quarters,  e.  g.^  by  R.  Heidenhain,^  E.  du  Bois-Reymond,^  Max 
Verworn,^  A.  Mosso,*  &c. 

All  the  objections  raised  by  these  authors  can  be  summed 
up  in  the  single  sentence  with  which  I  began  my  discussion  of 
the  subject,  viz.,  "  It  would  indeed  be  a  lack  of  intelligence  to 

^  Heidenhain,  Pflüger's  Archiv.,  vol.  xliii. ;  Suppl.,  pp.  61-64,  1888.  See  also 
my  reply  to  the  same,  Pflüger's  Archiv.,  vol.  xliv.  p.  270,  1889. 

2  E.  du  Bois-Reymond,  Sitzungsb.  d.  k.  preuss.  Akad.  d.  Wiss.  z.  Berlin, 
June  28,  1894. 

3  M.  Verworn,  "  Allgemeine  Physiologie,"  p.  50,  Jena,  1895. 

*  A.  Mosso,  Revue  Scientifique,  4th  series,  vol.  v.  p.  1,  Jan.  4,  1896. 


INTEODUCTION VITALISM    AND    MECHANISM  11 

expect,  with  the  same  senses,  to  make  discoveries  in  living 
nature  of  a  different  order  to  those  revealed  to  us  in  inorganic 
nature  "  (vide  p.  2). 

These  authors  have  left  untouched  the  central  point  of  the 
whole  question,  viz.,  the  impossibility  of  giving  a  mechanistic 
explanation  of  psychical  processes,  and  have  forgotten  that  these 
processes  form  the  immediate  object  of  our  experience,  the 
most  real  of  the  real. 

It  is  quite  open  to  any  one  who  objects  to  the  term  vitalism 
to  replace  it  by  another,  such  as  idealism,  scepticism,  empiri- 
cism ;  but  that  will  not  alter  my  contention.  I  have  only 
shown  how  the  metaphysical  speculations  and  dogmas  are  in 
direct  variance  with  the  immediate  results  of  observation  and 
experience,  i.  e.,  empirical  psychology.  The  hypotheses  on  which 
the  mechanistic  explanation  of  natural  phenomena  is  based, 
such  as  the  atomic  theory,  the  wave  theory  of  light,  the  mecha- 
nical theory  of  heat,  are  all  of  them  purely  metaphysical 
speculations,  i.  e.,  attempts  to  gain  an  insight  into  the  essential 
nature  of  things  as  they  are,  in  contradistinction  to  that  which 
they  appear  to  us  to  be.  Such  hypotheses  can  only  be  arrived 
at  by  projecting  certain  conceptions  of  our  inner  consciousness 
into  the  outside  world — conceptions  such  as  those  of  space, 
time,  quantity,  number,  force.  So  far  we  have  not  found  it 
any  advantage  to  project  in  this  way  other  of  our  conceptions, 
although  some  philosophers  have  made  such  an  attempt.  The 
physicist  wisely  limits  himself  to  measuring  the  quantity  of 
objects,  and  does  not  attempt  to  form  a  judgment  as  to  their 
quality. 

Now  however  the  mechanists  come  and,  crab-like,  reverse 
the  whole  process.  Having  begun  by  ascribing  certain  quali- 
ties, which  were  a  pure  product  of  their  inner  consciousness,  to 
external  things,  they  proceed  to  use  the  same  conceptions  to 
explain  all  vital  phenomena,  and  imagine  that  by  help  of  these 
threadbare  and  scanty  conceptions  they  have  explained  the 
manifold  activities  of  the  inner  world  of  consciousness. 

In  fact  we  have  no  grounds  for  assuming  that  our  internal 
world,  the  world  of  consciousness,  is  necessarily  and  entirely 
bound  up  with  certain  parts  of  the  brain.  For  we  must  re- 
member that  our  consciousness  arises  by  inheritance  through 
a  simple  cell,  from  which,  by  repeated  division,  all  the  cells 
and  tissues  of  our  body  are  derived,  including  those  of  the 
brain  and  cerebral  hemispheres,  and  other  parts  of  the  nervous 
system.  Now  the  history  of  the  evolution  of  function  must 
run  parallel  with  that  of  the  evolution  of  structure.  We  cannot 
indeed  suppose  that,  as  we  trace  the  animal  kingdom  down- 


12  LECTURE   I 

wards  to  the  unicellular  organisms,  the  conscious  life  of  the 
individual  ceases  at  that  exact  point  where  a  brain  is  no  longer 
present,  or  even  where  Ave  can  no  longer  make  out  a  specially 
differentiated  nervous  system.  May  it  not  be  possible  that 
every  cell  and  every  atom  is  really  a  conscious  being,  and  that 
all  life  is  conscious  life  ? 


LECTURE   II 

THE    CIRCULATION    OF    THE    CHEMICAL,    ELEMENTS^ 

The  object  of  physiological  chemistry  is  to  investigate  the 
chemical  processes  of  the  living  organism,  and  to  consider  the 
relation  of  these  processes  to  vital  phenomena.  We  shall  con- 
fine ourselves  to  a  consideration  of  these  processes  as  they  occur 
in  man  and  the  higher  animals.  It  may  appear  erroneous  to 
commence  the  study  of  the  most  complex  organisms  before 
obtaining  a  general  knowledge  of  the  chemical  processes  of  the 
more  simple  ;  but  since  no  physiological  chemistry  of  the  latter 
as  yet  exists,  there  is  no  choice  left  to  us.  The  little  that  is 
known  on  this  subject  will  be  introduced,  as  occasion  offers, 
when  we  come  to  discuss  the  metabolism  of  the  higher  animals. 

Before  we  approach  our  subject,  we  must  consider  the 
various  chemical  elements  and  forces  concerned  in  vital  mani- 
festations, as  they  present  themselves  in  organic  and  inorganic 
nature.  Nature  must  be  considered  as  a  whole  if  she  is  to  be 
understood  in  detail ;  there  must  be  a  clear  comprehension  of 
the  great  unchanging  laws  which  are  equally  applicable  to  liv- 
ing and  inanimate  things. 

Twelve  chemical  elements  enter  into  the  composition  of  all 
living  beings  without  exception  :  carbon,  hydrogen,  oxygen, 
nitrogen,  sulphur,  phosphorus,  chlorin,  potassium,  sodium, 
calcium,  magnesium,  and  iron. 

Carbojst  occurs,  on  the  surface  of  our  planet,  chiefly  united 
with  oxygen  in  the  form  of  carbonic  acid.  Of  this  only  a  small 
part  exists  free  in  the  atmosphere,  or  absorbed  in  water.  The 
greater  part  is  united  with  such  bases  as  lime  and  magnesia, 
and  forms  gigantic  strata  of  the  earth's  crust.  Only  a  com- 
paratively  small   amount  of  carbon  occurs  in  a  free  state  as 

^The  beginner  who  desires  to  make  himself  more  fully  acquainted  with  the 
subject  of  the  pi'esent  chapter  is  particularly  recommended  to  study  Liebig's  great 
work,  "  Chemistry  in  its  Applications  to  Agriculture  and  Physiology,"  1840,  8th 
edit.,  1865.  The  scientific  enthusiasm  which  our  great  teacher  imparted  during 
his  life  to  all  who  came  into  contact  with  him  still  speaks  from  every  page  of 
this  work.  Those  who  wish  to  familiarize  themselves  with  more  modem  achieve- 
ments should  read  Adolf  Meyer's  "Text-book  of  Agricultural  Chemistry" 
(Heidelberg,  1886) ,  in  which  will  be  found  a  full  account  of  the  original  literature 
on  the  subject. 

13 


14  LECTUEE    II 

coal,  and  a  still  smaller  quantity  as  graphite  and  diamond. 
Coal  is,  as  we  well  know,  the  residue  of  plants,  and  plants 
derive  their  carbon  from  the  carbonic  acid  of  the  atmosphere. 
Apart  then  from  graphite  and  diamond,  the  mode  of  formation 
of  which  is  still  unknown,  it  may  be  said  that  all  the  carbon 
on  the  earth  is  or  has  been  in  the  form  of  carbonic  acid,  and 
that  carbonic  acid  is  the  compound  through  which  carbon  must 
always  pass  in  its  innumerable  metamorphoses.  It  is  in  this 
form  that  carbon  appears  in  the  cycle  of  life ;  in  this  form 
alone  it  is  taken  up  by  plants  and  converted  into  the  numerous 
combinations  of  which  they  are  composed.  Carbon  is  intro- 
duced into  the  animal  organism  as  vegetable  food,  and  is 
excreted  either  as  carbonic  acid  or  in  the  form  of  compounds, 
such  as  urea,  which  very  rapidly  decompose  outside  the 
organism,  and  yield  carbonic  acid.  Carbon  then  leaves  the 
cycle  of  life  in  the  same  form  in  which  it  entered,  and  returns 
to  the  atmosphere  to  repeat  the  process  anew. 

Hydeogen  is  found  only  in  traces  as  a  free  gas.  In  in- 
organic nature  it  occurs  almost  exclusively  in  the  form  of 
water,  but  a  minute  quantity  appears  as  ammonia.  Hydrogen 
is  taken  up  by  plants  in  the  form  of  water  and  ammonia  only  ; 
it  enters  into  the  constitution  of  the  organic  compounds  of  the 
plants  which  serve  as  food  for  animals ;  it  leaves  the  animal 
organism  again  in  the  form  of  water  and  ammonia,  or  in  the 
shape  of  compounds  which  rapidly  split  up  into  these  two 
bodies. 

Oxygen  is  the  most  widely  distributed  of  all  elements  on 
the  surface  of  the  globe ;  it  forms  nearly  one-fourth  by  weight 
of  the  atmosphere,  eight-ninths  of  the  weight  of  water,  and 
about  half  the  weight  of  the  earth's  crust,  which  is  made  up 
almost  exclusively  of  oxygen-compounds.  Oxygen  is  the  only 
element  which  enters  the  living  organism  in  a  free  state,  but 
it  does  so  only  in  part,  and  in  the  case  of  plants  only  to  a  very 
small  extent.  The  chief  bulk  of  the  oxygen  enters  the  organi- 
zation of  plants  as  water  and  as  carbonic  acid.  By  the  aid  of 
sunlight,  the  plants  split  off  from  these  combinations  a  part  of 
the  oxygen,  and  form  compounds  richer  in  carbon  and  hydro- 
gen, which  as  food-stuffs  are  taken  into  the  animal  body,  where 
they  again  unite  with  oxygen,  and  are  returned  as  carbonic  acid 
and  water  to  the  air. 

By  this  antagonism  between  the  animal  and  vegetable  king- 
doms, the  balance  of  carbonic  acid  and  oxygen  is  maintained  in 
the  atmosphere  :  the  plant  yielding  the  oxygen  which  the  animal 
requires,  while  the  animal  in  its  turn  gives  out  the  carbonic  acid 
needed  by  the  plant. 


THE    CIRCULATION    OF    THE    CHEMICAL    ELEMENTS         15 

We  may  now  ask  whether  this  balance  will  always  be 
maintained.  Even  should  it  not  be  disturbed  by  vital  proc- 
esses, may  there  not  be  agents  at  work  in  inorganic  nature, 
which,  by  their  action  on  the  atmosphere,  may  increase  or 
diminish  those  of  its  constituents  necessary  to  existence  ? 

As  regards  carbonic  acid,  the  geologists  are  of  opinion  that 
there  was  formerly  a  larger  amount  in  the  atmosphere.  What 
are  the  causes  of  this  diminution  ?  are  they  still  at  work  ?  and 
have  we  to  look  forward  to  a  continuous  decrease  in  the  bulk  of 
this  gas  ? 

One  of  the  causes  of  the  diminution  of  carbonic  acid  is  not 
far  to  seek,  i.  e.,  the  formation  of  coal  strata  from  plants  which 
in  their  turn  have  derived  their  carbon  from  the  carbonic  acid 
of  the  atmosphere.  At  the  same  time,  the  amount  of  carbon 
taken  up  in  this  way  appears  to  be  comparatively  small.  And 
even  if  the  formation  of  coal  is  still  going  on  under  the  sea, 
on  the  other  hand  carbonic  acid  is  being  unceasingly  returned 
to  the  atmosphere  from  thousands  of  chimneys.  We  need 
scarcely  fear  a  diminution  of  carbonic  acid  from  this  cause. 
But  there  is  another  one  of  far  greater  importance :  I  mean 
the  displacement  of  the  silicic  acid  from  the  stone  of  the  earth's 
crust  by  the  carbonic  acid  of  the  atmosphere — the  union  of 
carbonic  acid  with  the  bases  previously  existing  as  silicates. 
The  rocks,  which  form  the  solid  crust,  consist  principally  of 
silicates  and  carbonates — of  compounds  of  silicic  and  carbonic 
acids  with  lime,  magnesium,  oxid  of  iron,  and  alkalies.  Now 
each  acid  is  always  trying  to  prevent  the  other  from  combining, 
and  to  unite  itself  with  the  basic  constituents.  Silicic  acid  and 
carbonic  acid  are  "the  two  great  powers  in  the  construction 
of  the  earth,"  and  are  always  at  war  with  each  other,  with 
alternate  victory  and  defeat  on  each  side.  As  soon  as  the  car- 
bonic acid  succeeds  in  obtaining  complete  mastery  over  the 
silicic  acid,  all  organic  life  must  cease  on  our  planet. 

The  chemical  affinity  of  carbonic  acid  to  the  basic  con- 
stituents of  the  rocks  is  closer  than  that  of  the  silicic  acid,  in 
the  cold  and  in  presence  of  water ;  the  carbonic  is  the  more 
powerful  acid  on  the  earth's  surface,  where  it  is  obtaining  a 
slow  but  sure  victory.  Every  wave  breaking  against  the  cliffs, 
every  ripple  which  washes  the  flinty  bed  of  the  river,  every 
drop  of  rain  which  falls  to  the  ground  contains  carbonic  acid  in 
solution,  and  slowly  but  surely  destroys  the  hardest  rock ;  the 
carbonic  acid  unites  with  the  basic  constituents,  and  the  dis- 
placed silicic  acid,  combined  with  the  residue  of  the  bases, 
sinks  to  the  bottom  of  the  water,  where  as  clay  or  sandstone 
it  gradually  forms  massive  strata  of  the  earth's  surface.     But 


16  LECTURE    II 

the  carbonic  acid,  united  with  lime  or  magnesium,  is  likewise 
precipitated,  mixed  either  with  part  of  the  decomposed  silicates 
in  the  form  of  marl,  or  in  separate  strata  as  limestone  and 
dolomite.  Half  the  entire  weight  of  the  thick  calcareous  strata, 
which  compose  a  very  large  part  of  the  earth's  crust,  consists  of 
carbonic  acid,  derived  from  the  atmosphere,  and  which  has 
apparently  been  withdrawn  for  ever  from  the  cycle  of  life. 

But  the  struggle  between  the  two  acids  wears  another 
aspect  in  the  interior  of  the  earth.  At  the  higher  temperature 
which  prevails  there,  the  silicic  acid  is  the  more  powerful.  In 
the  depths  of  the  earth  it  attacks  the  carbonates,  and  the 
carbonic  acid  which  is  driven  off  escapes  into,  the  atmosphere. 
This  carbonic  acid  is  continually  issuing  from  all  active  vol- 
canoes, and  also  from  other  cracks  and  fissures  in  various  parts 
of  the  earth.  The  quantity  which  is  thus  returned  to  the 
atmosphere  cannot  be  determined,  but  it  seems  probable  that 
it  is  much  less  than  what  is  constantly  being  removed  in  the 
form  of  chalk  and  carbonate  of  magnesia.  If  it  is  true  that 
our  planet  is  steadily  becomiug  cooler  and  its  crust  thicker,  the 
factor  which  aids  the  silicic  acid,  the  warmth  of  the  earth  itself, 
must  continually  decrease,  and  thus  leave  nothing  to  dispute 
the  rule  of  carbonic  acid ;  hence  organic  life  must  terminate. 

In  like  manner  as  carbonic  acid,  a  second  constituent  of  the 
atmosphere,  oxygen,  is  constantly  becoming  fixed  in  the  crust 
of  the  earth,  and  thus  removed  from  the  cycle  of  vital  phe- 
nomena. The  constituent  of  the  earth's  crust  which  binds  it 
is  the  ferrous  oxid  resulting  from  the  decomposition  of  certain 
silicates.  This  becomes  oxidized  to  ferric  oxid,  which,  as  is 
well  known,  forms  by  itself  considerable  strata,  and  occurs  in 
still  larger  quantities  mixed  with  other  materials,  as  clay,  loam, 
sandstone,  and  shale.  One-third  of  the  oxygen  in  these  huge 
masses  of  ferric  oxid  is  derived  from  the  atmosphere.  A  part 
of  this  oxygen  may  return  to  the  atmosphere,  for,  when  the 
oxid  of  iron  comes  into  contact  with  decomposing  organic 
substances,  the  latter  abstract  part  of  its  oxygen.  As  a  result 
of  the  oxidation  of  the  organic  substances,  carbonic  acid  is 
returned  to  the  atmosphere,  where  it  may  again  be  decomposed 
by  plants,  thus  liberating  oxygen.  But  this  activity  of  plants 
is  the  only  process  by  which  oxygen  is  set  free  on  the  earth's 
surface,  and  it  is  very  questionable  whether  it  is  of  itself 
sufficient  to  counterbalance  the  consumption  of  oxygen  in 
respiration,  putrefaction,  combustion,  and  oxidation  of  the 
compounds  of  iron  and  sulphur. 

It  thus  appears  that  a  substance  of  great  importance  in  the 
nutrition  of  plants,  free  carbonic  acid,  and  a  substance  essential 


THE    CIECULATIOX    OF    THE    CHEMICAL    ELEMENTS  17 

to  the  maintenance  of  all  organic  life,  free  oxygen,  are  contin- 
ually diminishing,  and  that  the  time  is  slowly  but  surely  ap- 
proaching when  the  conditions  necessary  for  our  existence  will 
no  longer  prevail,  and  when  all  life  will  become  extinct  on  this 
planet. 

We  will  now  turn  our  attention  to  the  niteogex,  the  fourth 
and  last  of  the  elements  which  organic  nature  derives  from  the 
atmosphere  directly  or  indirectly.  Nitrogen  is  characterized 
by  its  small  affinity  for  other  elements.  For  this  reason  the 
greater  part  of  the  nitrogen  is  found  in  a  free  state ;  it  forms 
four-fifths  of  the  atmosphere.  Only  a  minute  portion  is  found 
in  inorganic  nature  in  the  form  of  compounds  :  this  is  the 
nitrogen  of  ammonia,  and  of  its  products  of  oxidation,  nitrous 
and  nitric  acids.  Nitrogen  enters  organic  nature  in  the  form  of 
these  compounds  only.  The  great  bulk  of  free  nitrogen  has 
no  part  in  vital  processes,  for  the  plant  cannot  assimilate  it. 
So  far  the  assimilation  of  atmospheric  nitrogen  has  been  proved 
to  occur  only  in  certain  bacteria. 

Now,  since  the  quantity  of  fixed  nitrogen  existing  in  nature 
is  very  small,  and  since  plants  cannot  utilize  the  other  constit- 
uents of  their  food  unless  an  appropriate  quantity'  of  fixed 
nitrogen  be  taken  up  at  the  same  time,  it  is  obvious  that  the 
total  number  of  organic  beings  which  can  simultaneously  exist 
on  the  earth  must  depend  in  the  first  instance  on  the  amount  of 
fixed  nitrogen  available.  It  is  therefore  a  question  of  the  great- 
est interest  to  know  by  what  means  the  amount  of  fixed  nitrogen 
is  increased  or  diminished. 

The  process  of  life  itself  does  not  alter  the  sum  total  of  fixed 
nitrogen.  Nitrogen  is  taken  up  by  the  plants  as  ammonia,  ni- 
trites, and  nitrates,  and  is  converted  into  and  forms  part  of  nu- 
merous and  most  complicated  substances,  chiefly  proteids.  In 
the  latter  form  it  enters  the  animal  economy,  where  the  proteid 
breaks  do^vn  into  urea,  uric  acid,  and  other  compounds,  which 
rapidly  decompose  outside  the  organism  and  yield  ammonia. 

The  bacteria  mentioned  above  form  an  exception  to  this  rule. 
On  the  roots  of  leguminosse  we  may  find  small  nodules,  which 
are  produced  by  an  infection  with  certain  bacteria,  the  two 
organisms,  plant  and  bacteria,  being  symbiotic.  If  the  legu- 
minosas  are  grown  on  a  sterilized  soil  these  nodules  are  not 
formed,  and  the  plants  attain  only  a  slow  and  imperfect  de- 
velopment, the  amount  of  proteid  formed  in  them  being 
abnormally  small.  If  however  the  soil  be  inoculated  with 
the  proper  species  of  bacterium,  the  nodules  soon  make  their 
appearance ;  the  plants  grow  luxuriantly,  and  form  large 
quantities  of   proteid    out  of  the    combined    nitrogen  of    the 

2 


18  LECTURE   II 

soil.^  It  might  have  been  expected  that  other  microorganisms 
might  have  been  found  to  possess  the  same  properties.  Up  to 
the  present,  however,  only  one  other  species  of  bacterium,  the 
Clostridium  pasteurianum,  has  been  found  to  possess  the  capacity 
of  fixing  free  nitrogen.^ 

But  in  inorganic  nature  there  must  be  factors  at  work 
which  produce  fixed  nitrogen.  Such  a  process  has  been  rec- 
ognized in  atmospheric  electrical  discharges.  It  has  been 
established  by  numerous  experiments  that,  by  means  of  electric 
discharges,  nitrogen  is  united  with  oxygen  to  form  nitric  acid, 
and  that,  by  sending  electric  sparks  through  a  damp  atmos- 
phere, nitrogen  and  aqueous  vapour  combine  to  form  nitrate  of 
ammonia.^ 

2N4-2H20  =  NH4NOi, 

This  process  occurs  on  a  large  scale  in  every  thunderstorm, 
the  products  being  conveyed  to  the  ground  by  the  rain. 
Schönbein  has  pointed  out  a  second  process,  viz.,  that  wherever 
evaporation  occurs,  minute  traces  of  nitrite  of  ammonia  are 
formed  in  the  air.  The  evaporation  which  is  constantly  going 
on  from  the  surface  of  the  plants  themselves,  may  therefore  be 
a  source  of  combined  nitrogen  for  them. 

It  follows  that  the  whole  store  of  fixed  nitrogen  is  con- 
stantly increasing  from  various  sources.  Organic  life  would 
therefore  develop  with  ever  greater  luxuriance  were  it  not 
for  the  operation  of  other  causes,  by  means  of  which  combined 
nitrogen  is  again  set  free.  This  is  efiected  by  combustion. 
The  burning  up  of  vast  forests  of  wood  by  man,  which  has 
been  going  on  for  thousands  of  years,  detracts  from  the  store  of 
fixed  nitrogen,  to  which  animals  and  plants  owe  their  exist- 
ence ;  the  total  of  life  is  no  doubt  diminished  thereby,  and  the 
fertility  of  the  soil  must  decrease.  For  this  reason  the  pro- 
ject of  cremation,  recently  introduced,  should  be  abandoned, 
although  the  amount  of  fixed  nitrogen  destroyed  in  this  manner 
would  be  much  less  than  it  is  in  consuming  forests  as  fuel. 
Combined  nitrogen  is  further  destroyed  by  igniting  gunpowder 
or  other  explosives,  which  are  all  derivatives  of  nitric  acid.  In 
this  sense   it    may  be  affirmed    that  every    shot   from  a  fire- 

^  W.  O.  Atwater  and  C.  D.  Woods,  Amer.  Chem.  Journ.,  vol.  vi.  p.  365, 1884 
vol.  xii.    p.  256,  1890;  vol.  xiii.  p.  42,  1891.    H.  Hellriegel  and  H.  Willfarth 
"Unters,   üb.  d.  Stickstoffnahrung  d.  Gramineen  u.  Leguminosen."      Berlin, 
1888.    This  discovery  has  been  repeatedly  confirmed  by  experiments  of  Beyer- 
ink,  B.  Frank,  Breal,  Berthelot,  Nobbe,  and  others. 

2  S.  Winogradsky,  Arch.  d.  Sei.  Mol.,  St.  Petersburg,  vol.  iii.  p.  297,  1895. 

'Berthelot,  Bull.  Soc.  Chim.  (2),  t.  xxvii.  p.  338;  Ann.  Chim.  Phys.  (5),  t. 
xii.  p.  445,  1877. 


THE    CIECULATION    OF    THE    CHEMICAL    ELEMENTS  19 

arm  kills,  that  it  destroys  life  whether  the  ball  strikes  a  living 
being  or  not.  For  no  life  is  lost  by  the  death  of  the  individual ; 
from  the  decay  of  the  body  equivalent  new  life  arises.  But 
the  destruction  of  combined  nitrogen  means  the  definite  dimi- 
nution of  the  capital,  upon  the  amount  of  which  the  total  num- 
ber of  living  beings  depends. 

These  views  of  mine  have  been  objected  to  on  the  grounds 
that  certain  bacteria  have  the  power  of  fixing  nitrogen,  so  that 
the  burning  of  forests  and  dead  bodies  cannot  be  regarded  as  a 
spoliation  of  the  capital  of  life.  This  is  analogous  to  saying 
that  a  man  may  be  robbed  if  he  is  going  to  inherit  property. 
The  formation  and  the  destruction  of  fixed  nitrogen  are  not 
mutually  dependent  processes.  An  increase  in  destruction 
does  not  imply  an  increase  in  formation,  and  the  sum  of  life  is 
therefore  diminished.  So  long  as  there  are  fields  where  the 
ammonia  of  the  soil  is  at  a  minimum,  so  long  must  the  burn- 
ing of  plants  and  animals  be  regarded  as  a  spoliation  of  living 
nature. 

In  the  world  about  twenty  men  per  thousand  die  every  year, 
so  that  in  fifty  years  the  total  number  of  deaths  corresponds 
approximately  to  the  total  number  of  inhabitants  on  the  globe, 
i.  e.,  about  ten  human  beings  to  every  square  kilometer  of  land. 
(The  total  area  of  land  on  the  earth's  surface  is  135  million 
square  kilometers,  and  the  total  number  of  inhabitants  about 
1500  millions.)  Thus  if  all  dead  bodies  were  burnt,  they 
would  amount  in  fifty  years  to  ten  per  square  kilometer,  and 
in  5000  years  to  1000  corpses.  Can  it  be  imagined  that  such 
a  process  would  have  no  eifect  on  the  fertility  of  the  soil? 
Adolf  Meyer,  in  his  "  Text-book  of  Agricultural  Chemistry  " 
(part  ii.  p.  303,  1886),  states  that  already  it  is  no  longer 
possible  to  obtain  a  proper  yield  from  our  cultivated  lands  with- 
out recourse  to  artificial  manures  containing  combined  nitrogen. 

All  the  arguments  which  have  been  brought  forward 
against  burial  are  really  only  applicable  to  the  interment  of 
a  number  of  bodies  in  a  confined  space,  such  as  a  churchyard, 
and  have  no  weight  against  the  only  rational  mode  of  disposal 
of  the  dead,  viz.,  their  distribution  as  widely  as  possible  over 
the  woods  and  fields.  With  all  our  improved  means  of  com- 
munication this  should  be  an  easy  task.  The  contamination  of 
our  water  by  dead  bodies  is  negligible  compared  with  that 
from  sewage.  It  is  absurd  to  cremate  only  the  smaller  part, 
and  if  we  begin  to  destroy  by  combustion  our  excreta  as  well 
as  our  dead  bodies,  there  will  soon  be  a  perceptible  loss  of  fer- 
ility  to  the  soil. 

The  remaining   eight  elements  are  derived  by  the  plant 


20  LECTURE    II 

from  the  soil.  Sulphur  is  widely  distributed  in  inorganic 
nature  as  sulphates  of  the  alkalies  and  alkaline  earths.  It 
enters  the  vegetable  organism  in  this  form,  and  takes  part  in 
the  building  up  of  the  proteid  molecule,  in  which  it  amounts 
to  about  0.3  to  2  per  cent,  of  the  weight.  It  is  chiefly  taken 
up  by  the  animal  organism  in  the  form  of  proteid,  and  is 
excreted  for  the  most  part  in  the  highest  oxidized  condition  as 
sulphuric  acid,  derived  from  the  splitting  up  and  oxidation 
of  the  proteid  molecule.  In  this  form,  united  with  alkalies, 
it  is  again  ready  to  repeat  the  cycle  of  life. 

The  course  of  phosphorus  is  very  similar.  It  occurs  in  the 
inorganic  world  only  in  a  high  state  of  oxidation  as  phosphoric 
acid  united  with  bases,  esj)ecially  with  alkalies  and  alkaline 
earths,  and  enters  the  plant  only  in  this  form. 

Although  phosphoric  acid  is  widely  distributed  over  the 
whole  surface  of  the  globe,  its  amount  in  most  soils  is  very 
small.  As  in  the  case  of  nitrogen,  the  quantity  present  in  a 
field  may  be  so  little  that  vegetable  life  is  unable  to  convert 
all  the  other  elements  into  food.  In  rare  cases  this  is  also 
true  of  potassium  ;  but  there  is  never  a  lack  of  the  remaining 
nutrient  substance.  In  agriculture  it  is  therefore  of  the  greatest 
importance  to  determine  which  of  these  three  elements  is  most 
deficient  in  any  given  soil.  The  fertility  of  the  land  will 
depend  on  the  quantity  of  the  substance  of  which  there  is 
a  minimum.  This  is  the  important  law  which  agricultural 
chemistry  designates  as  the  "  Law  of  the  Minimum."  The 
element  which  is  present  in  the  smallest  quantity  must  be 
supplied  to  the  soil  by  artificial  manuring.  It  is  generally 
phosphoric  acid ;  hence  the  use  of  bone-dust,  apatite,  and  the 
like. 

In  the  plant,  phosphoric  acid  takes  part  in  the  formation 
of  very  complicated  combinations — of  the  various  forms  of 
lecithin  and  nuclein,  which  are  integral  constituents  of  every 
vegetable  and  animal  cell.  It  is  chiefly  in  these  combinations, 
and  only  to  a  small  extent  as  salts,  that  phosphorus  enters  the 
animal  body,  which  it  leaves  in  the  same  form  that  it  entered 
the  plant — as  a  phosphate. 

The  circulation  of  chlorin  is  very  simple ;  it  occurs  in 
nature  only  in  the  form  of  salts,  chiefly  united  with  sodium  and 
potassium.  In  this  form  it  enters  and  leaves  the  cycle  of  life. 
It  takes  no  part  in  the  formation  of  organic  compounds. 

The  same  is  true  of  sodium,  potassium,  calcium,  and 
magnesium.  They  occur  in  the  inorganic  world  only  as  salts, 
enter  plants  as  such,  combine  very  loosely  with  organic  matter, 
and  are  excreted  from  the  animal  body  also  in  the  form  of  salts. 


THE    CIRCULATION    OF    THE    CHEMICAL    ELEMENTS  21 

Iron  never  occurs  on  the  surface  of  the  globe  as  a  free 
metal,  but  chiefly  in  union  with  oxygen  as  ferrous  and  ferric 
oxides.  The  former  is  a  strong  base,  and  forms  neutral  salts 
with  all  acids.  Ferric  oxid  is  only  a  weak  base,  and  is  unable 
to  fix  carbonic  acid.  Ferrous  silicates,  when  decomposed  by 
atmospheric  carbonic  acid,  yield  ferrous  carbonate,  which  is 
soluble  in  water  containing  carbonic  acid,  and  is  distributed  by 
water  all  over  the  earth.  But  as  soon  as  it  comes  in  contact 
with  the  atmosphere,  it  is  oxidized  to  ferric  oxid,  and  the 
carbonic  acid,  being  set  free,  is  returned  to  the  atmosphere. 
The  ferric  oxid,  when  it  comes  in  contact  with  decomposing 
organic  matter,  is  reduced,  and  ferrous  carbonate  is  again 
formed  and  carried  oif  by  water,  until  it  again  comes  in 
contact  with  air,  and  again  aids  in  the  oxidation  of  vegetable 
and  animal  refuse.  Iron  is  therefore  an  indefatigable  oxidizing 
agent.  The  iron  prevents  the  retention  of  carbon  in  the  soil, 
and  enables  it  to  return  to  the  atmosphere,  and  thus  to  reenter 
the  cycle  of  life. 

The  process  of  oxidation  is  rather  more  complicated  when 
sulphur  is  present.  Sulphur  also  acts  as  a  carrier  of  oxygen. 
If  decomposing  organic  substances  meet  simultaneously  with 
oxids  of  iron  and  sulphates,  e.  g.,  gypsum,  not  only  is  the 
oxygen  of  the  oxids  completely  taken  up,  but  that  also  of  the 
sulphuric  acid,  sulphid  of  iron  being  formed.  The  latter,  in 
the  presence  of  air,  may  again  be  oxidized  to  sulphuric  acid 
and  ferric  oxid,  and  then  again  act  as  an  oxidizing  agent.  The 
sulphur  required  for  the  formation  of  sulphid  of  iron  after  the 
reduction  of  ferric  oxid,  may  be  yielded  by  decomposing 
organic  matter  itself,  since  this  always  contains  proteid  and 
consequently  sulphur.  In  fact  the  organic  sulphur  compounds 
have  themselves  been  formed  in  plants  by  the  reduction  of 
sulphates. 

Iron  plays  the  same  part  m  our  organism  as  it  does  in  the 
earth's  crust,  the  part  of  oxygen-carrier.  Only  the  iron  in  our 
organism  does  not  occur  as  ferric  and  ferrous  oxids,  but  as  a 
complex  organic  compound,  the  most  complicated  body  wliich 
has  hitherto  been  investigated  with  precision,  and  which  con- 
tains at  least  seven  hundred  atoms  of  carbon  in  its  molecule. 
This  is  the  red  coloring  matter  of  the  blood,  hemoglobin, 
which,  as  oxy-hemoglobin,  a  loose  compound  with  oxygen, 
corresponds  to  the  ferric  oxid,  and,  as  reduced  hemoglobin,  to 
ferrous  oxid.  Hemoglobin  also  contains  sulphur,  and  it  may 
be  that  the  sulphur  of  hemoglobin,  and  of  all  other  proteid 
bodies,  still  retains  its  function  as  an  oxidizing  agent.  At  any 
rate,  it  cannot  be  to  the  iron  alone  that  this  property  is  due, 


22  LECTURE   II 

since,  as  we  shall  see  in  the  seventeenth  lecture,  the  amount  of 
loosely  combined  oxygen  is  much  too  large. 

The  enormous  size  of  the  hemoglobin  molecule  finds  a  teleo- 
logical  explanation  if  we  consider  that  iron  is  eight  times  as 
heavy  as  water.  A  compound  of  iron  which  would  float  easily 
along  with  the  blood-current  through  the  vessels  could  only 
be  secured  by  the  iron  being  taken  up  by  so  large  an  organic 
molecule. 

Hemoglobin  first  makes  its  appearance  in  the  animal 
organism.  It  does  not  exist  in  plants.  The  plant  has  the 
power  of  assimilating  inorganic  compounds  of  iron,  and  of 
using  them  for  building  up  complex  organic  compounds,  which 
have  not  yet  been  sufficiently  investigated.  From  these 
bodies  the  hemoglobin  is  produced  in  the  animal  economy 
(vide  Lecture  XXV.). 

Iron  likewise  plays  an  important  part  in  vegetable  life  ;^ 
we  know  that  chlorophyl  granules  cannot  be  formed  without 
it.  If  plants  are  allowed  to  grow  in  nutritive  solutions  free 
from  iron,  the  leaves  are  colorless,  but  become  green  as  soon 
as  an  iron  salt  is  added  to  the  fluid  in  which  the  roots  are  im- 
mersed. It  is  even  sufficient  merely  to  brush  the  surface  of 
the  colorless  leaf  with  a  solution  of  an  iron  salt  to  cause  the 
appearance  of  the  green  color  in  the  part  thus  painted. 
Chlorophyl  itself  contains  no  iron,  and  we  do  not  know  in 
what  way  the  iron  is  concerned  in  its  production.  It  seems 
however  that  there  is  a  proportionality  between  the  amount 
of  iron  and  that  of  chlorophyl  in  any  given  part  of  the  plant. 
Thus  Boussingault  ^  found  .0039  per  cent.  Fe  in  the  green 
leaves  of  a  cabbage,  while  the  inner  etiolated  leaves  contained 
only  0.0009  per  cent.  Fe. 

It  is  not  yet  known  in  what  form  and  by  what  path  iron 
leaves  the  animal  body.  Urine  contains  scarcely  perceptible 
traces  of  iron,  probably  as  an  organic  compound.  The  feces 
always  contain  a  considerable  quantity  of  sulphid  of  iron. 
But  it  cannot  be  determined  how  much  of  this  is  derived  from 
the  food,  and  how  much  from  the  digestive  secretions.  Outside 
the  body,  the  sulphid  of  iron  is  converted  by  the  atmospheric 
oxygen  into  sulphuric  acid  and  oxid  of  iron,  and  the  cycle  is 
complete. 

In  addition  to  the  twelve  elements  alluded  to,  the  follow- 
ing elements  are  met  with  in  certain  organisms,  though  they 

^  Molisch  ("  Die  Pflanze  in  ihren  Beziehungen  zum  Eisen  ")  gives  an  account 
of  the  botanical  literature  on  the  relations  of  iron  in  plants. 

2  Boussingault,  CorniH.  rend.,  vol.  Ixxiv.  p.  1356:  1872;  E.  Häusermann, 
Zeitschr.  f.  2)hysiolog.  C'hem.,  vol.  xxiii.  p.  587:  1897. 


THE    CIRCULATION    OF    THE    CHEMICAL    ELEMENTS  23 

are  not  always  an  integral  part  of  their  composition  :   silicon, 
fluorin,  bromin,  iodin,  aluminium,  manganese,  and  copper. 

Silicon  does  not  occur  in  the  free  state,  but  only  as  silicic 
acid.  This  compound,  as  already  mentioned,  is  amongst  the 
most  widely  distributed  bodies  in  the  earth's  crust.  The  alkaline 
salts  of  silicic  acid  are  soluble  in  water,  and  the  free  acid,  when 
liberated  by  carbonic  acid  from  certain  silicates,  at  first  appears 
as  a  hydrated  acid  apparently  in  a  state  of  solution,  in  what  is 
known  as  a  colloid  condition  (see  Lecture  IV.).  Probably 
plants  absorb  silicic  acid  in  both  these  forms.  All  the  higher 
plants  seem  to  contain  silicic  acid.  Among  cryptogamic  plants, 
the  reeds  and  grasses  are  distinguished  by  the  large  amount  of 
silicic  acid  they  contain.  Certain  unicellular  algse  (the  Dia- 
tomacese)  cover  themselves  with  a  shell  of  silica.  Silicic  acid 
is  said  to  be  absent  from  the  ash  of  certain  fungi. 

But  it  would  not  appear  that  silicic  acid  plays  any  im- 
portant part  in  the  economy  of  the  higher  plants.  This  is 
shown  by  the  following  experiments  on  the  graminacese,  which 
are  rich  in  silicon,  as  wheat,  oats,  maize,  barley.  When  these 
plants  are  allowed  to  germinate  in  nutrient  fluids  free  from 
silica,  so  that  they  can  only  obtain  mere  traces  of  silicic  acid 
from  the  glass  vessel  containing  the  solution,  they  develop 
completely,  and  pass  through  a  perfectly  normal  course  of  life. 
In  the  ash  of  maize  grown  in  this  way,  only  0.7  per  cent,  of 
silicic  acid  was  found,  whilst,  under  ordinary  conditions  of 
growth,  20  per  cent,  is  the  average  quantity.^ 

Whether  silicon  exists  in  plants  only  as  silicic  acid,  or 
whether  it  forms  more  complex  compounds,  has  not  been 
ascertained.  Silicon  is  a  tetravalent  element,  like  carbon. 
Silicic  acid  is  quite  analogous  in  its  composition  to  carbonic 
acid.  Hence  a  probability  that  silicon  could  form  numerous 
compounds  which  would  bear  the  same  relation  to  silicic  acid 
as  the  organic  compounds  do  to  carbonic  acid  ;  and,  as  a  matter 
of  fact,  Friedel  and  Ladenburg  ^  have  succeeded  in  preparing  a 
series  of  such  compounds.  But  their  existence  in  plants  has, 
up  to  the  present  time,  not  been  detected.^ 

Silicic  acid  is  taken  up  by  animals  in  the  form  of  vegetable 
food.  It  is  absorbed  by  the  alimentary  canal,  and  passes 
through  all  the  tissues ;   hence  minute  traces  can  be  demon- 

1  Sachs,  "  Flora,"  p.  52 :  1862 ;  and  Wochenblatt  der  Annalen  der  Landioirth- 
Schaft,  p.  184 :  1862. 

2  C.  Friedel  and  A.  Ladenburg,  Compt.  rend.,  vol.  Ixvi.  p.  816 :  1868 ;  and 
vol.  Ixviii.  p.  920 :  1869.  Ber.  d.  deutsch,  ehem.  Ges.,  p.  901 :  1871 ;  and  pp. 
319,  1081 :  1872. 

3  Ladenburg,  £er.  d.  deutsch,  ehem.  Ges.,  vol.  v.  p.  568 :  1872 ;  W.  Lange, 
ibid.,  vol.  xi.  p.  822:  1878. 


24  LECTURE    II 

strated  in  every  organ.  It  is  contained  in  considerable  quantity 
in  the  urine  of  herbivorous  animals,  and  in  sheep  sometimes 
occasions  stone  in  the  bladder.  It  appears  however  to  be  of 
importance  only  in  the  development  of  hairs  and  feathers/  the 
asb  of  which  is  always  rich  in  silicic  acid.  The  constant  pres- 
ence of  silicic  acid  in  eggs  points  to  its  being  essential  in  the 
development  of  birds. 

Fluorin  has  been  found  in  very  small  quantity  in  some 
plants  and  anhnals.  It  is  difficult  to  detect/  and  it  may 
possibly  be  more  widely  existent  in  organic  nature  than  has 
been  suspected.  It  is  invariably  found  in  the  bones  and  teeth 
of  men  and  mammals,  although  Ave  have  not  yet  succeeded  in 
ascertaining  the  exact  amount  by  our  present  methods.  It  is 
also  said  to  have  been  detected  in  the  blood  of  mammals  and 
of  birds. ^  Recently,  G.  Tammann,"*  by  means  of  careful  deter- 
minations, has  found  .001  per  cent,  fluorin  in  the  yolk  of  eggs, 
.0007  per  cent,  in  calves'  brains,  and  .0003  grms.  in  one  liter 
of  cow's  milk.  In  3000  ccm.  of  cow's  blood,  the  presence  of 
fluorin  could  be  qualitatively  detected.  Small  quantities  of 
fluorin  are  distributed  everywhere  in  the  earth,  in  the  form 
of  fluorspar  and  apatite ;  therefore  plants  are  never  without  it. 
It  acts  perhaps  differently  in  the  nutrition  of  men  and  animals. 
It  would  be  very  interesting  to  have  the  exact  amount  of 
fluorin  in  our  food  determined,  and  also  the  quantity  we  really 
need  of  it.  At  any  rate,  the  above-mentioned  "  law  of  the 
minimum "  holds  good  for  animal  as  well  as  for  vegetable 
growth.  It  is  conceivable  that  milk,  although  rich  in  the  most 
important  substances  of  nutrition,  might  yet  be  useless  for 
the  growth  of  the  infant,  for  want  of  the  necessary  trace  of 
fluorin. 

Bromin  and  lODiisr  are  present  in  many  kinds  of  sea- 
weed, and  thus  pass  into  the  system  of  marine  animals.  A 
collected  account  of  the  organisms  containing  iodin,  which 
have  been  utilized  for  therapeutic  purposes,  has  recently  been 
published  by  E.   Harnack.^     The  horny  axial  skeleton  of  a 

^  [It  is  interesting  to  note  that  Drechsel,  in  his  last  published  paper,  has 
described  an  organic  silicon  compound,  viz.,  a  cliolesterin  ester  of  silicic  acid,  as 
occurring  in  birds'  feathers.  This  is  the  first  organic  silicon  compound  which 
has,  so  far,  been  found  to  occur  in  nature.  Centralbl.  f.  Physiol.,  vol.  xi.  pp. 
361-363:   1897.] 

^See  G.  Tammann,  Zeitschr.  f,  analyt.  Chem.,  vol.  xxiv.  p.  328:  1885,  where 
an  account  of  the  literature  on  the  methods  of  detecting  fluorin  will  also  be 
found. 

^G.  Wilson,  Trans,  of  the  Brit.  Ass.  for  the  Adv.  of  Sei.,  p.  67:  1851; 
and  J.  Nicies,  Compt.  rend.,  vol.  xliii.  p.  885  :  1856. 

*G.  Tammann,  Zeitschr.  f.  physiol.  Chem.,  vol.  xii.  p.  322:  1888. 

^E.  Harnack,  Munch,  med.  Wochenschr.,  No.  9:  1896. 


THE    CIRCULATION    OF    THE    CHEMICAL    ELEMENTS  25 

species  of  coral  ( Gorgonia  ^ )  is  rich  in  iodin,  part  of  which 
at  any  rate  is  in  organic  combination.  Iodin  is  however  also 
contained  in  small  quantities  in  many  land  plants  as  well  as 
in  fresh-water  animals,  such  as  the  fresh-water  sponges  (Spongia 
*fluviatiUs). 

Universal  attention  has  recently  been  attracted  by  Baumann's, 
discovery  of  iodin  in  the  thyroid  gland  of  men,  sheep,  pig,, 
and  apparently  many  other  mammals.^  Further  investiga- 
tions have  shown  that  iodin  is  also  contained  in  the  thymus,^; 
the  spleen,  and  the  pituitary  body  of  man,^  and  in  the  ovaries  ^• 
of  the  cow  and  pig.  In  all  the  animal  and  vegetable  organisms- 
just  mentioned,  the  iodin  is  present  for  the  greater  part  as  an, 
organic  compound,  although  only  the  iodin  compound  of 
Gorgonia  has  been  hitherto  isolated  as  a  chemical  individual  in, 
a  crystalline  form.''  This  compound  is  an  acid  of  the  compo- 
sition C^H-,]S[IO,.  Drechsel  suggests  that  it  is  an  amido-iodo- 
butyric  acid,  and  has  proposed  to  call  it,  for  the  present,  iodo- 
gorgonic  acid. 

We  know  absolutely  nothing  as  to  the  significance  of  iodin 
for  any  vital  functions. 

Aluminium  is  one  of  the  elements  most  frequently  met 
with.  Its  sesquioxide,  alumina,  is  found,  united  with  silicic 
acid,  in  almost  all  crystalline  rocks  which  form  the  larger 
portion  of  the  great  mountain  ranges.  Mixed  with  the  prod- 
ucts of  disintegration  of  these  rocks  it  is  found  everywhere 
in  ample  quantity  in  the  soil.  It  is  therefore  very  remarkable 
that  alumina  takes  little  or  no  part  in  the  metabolism  of  living 
beings.  It  has  been  shown  positively  to  exist  in  any  noticeable 
quantity  only  in  a  few  plants,  especially  in  a  few  kinds  of 
lycopodium,  in  the  ash  of  which  it  amounts  to  over  57  percent. 
We  do  not  know  whether  it  is  essential  for  these  plants,  nor  of 
what  use  it  is  to  them  ;  no  experiments  have  yet  been  made  to 
decide  this  question.  Alumina  has  not  yet  been  detected  in  the 
animal  body. 

Manganese  is  found  in  considerable  quantity  in  the  ash  of 
a  few  plants,  although  nothing  is  known  concerning  its  sig- 
nificance in  vital  processes.  Traces  of  this  metal  are  found  all 
through  the  vegetable  kingdom,  and  occasionally  in  the  animal 
body. 

IE.  Drechsel,  Centralbl.  f.  Physiol.,  vol.  ix.  p.  704;  1895;  and  Zeitschr.  f. 
Biolog.,  vol.  xxxiii,  p.  96  :  1896. 

2  Compare  Lecture  XXIX. 

*  Baumann,  Munch,  med.  Wochenschr.,  No.  14  :  1896. 

*Schnitzleru.  Ewald,  Wien.  klin.  Wochenschr.,  l^o.  29:  1896. 

^Schaerges,  Pharm.  Zeitg.,  No.  71:  1896;  and  E.  Barell,  idem,  No.  15: 
1897. 

^  Drechsel,  loc.  cit. 


26  LECTURE    II 

Minute  traces  of  most  of  the  other  metals  are  occasionally 
fomid  in  plants  and  animals.  They  should  not  on  that  account 
be  considered  as  essential  constituents. 

The  presence  of  copper  in  the  blood  of  certain  cephalopods 
and  Crustacea  is  noteworthy.  This  metal  appears  to  be  present ' 
in  the  form  of  an  organic  compound,  and  to  serve  as  oxygen- 
carrier,  thus  playing  a  part  similar  to  that  of  the  iron  in  hemo- 
globin. The  blood  of  these  animals  is  blue,  but  loses  its  color 
as  soon  as  the  oxygen  is  withdrawn  either  by  pumping,  by. the 
passage  of  a  stream  of  an  indifferent  gas,  or  by  the  action  of  re- 
ducing agents.  When  shaken  up  with  air  the  blood  again  be- 
comes blue.  The  latest  experiments  on  this  subject  have  been 
carried  out  by  Fr6d§ricq,^  whose  essay  also  contains  an  account 
of  the  work  done  by  his  predecessors. 

1  Leon  Fredericq,  Bulletins  de  Vac.  roy.  de  Belgique,  ser.  ii.  t.  xlvi.  No.  11 : 
1878;  Comp«.  re?id.,  t.  Ixxxvii,  p.  996:  1878. 


LECTURE   III 


CONSERVATION    OF    ENERGY 


Most  intimately  connected  with  the  circulation  of  the  ele- 
ments is  the  circulation  of  energy.  The  latter  is  not  however 
limited  to  this  earth ;  it  streams  on  to  our  planet  with  the 
sunlight,  and,  having  run  its  course  through  plant  and  animal 
life,  streams  back  again  into  illimitable  space. 

It  is  as  impossible  to  destroy  energy  as  matter.  Energy 
itself  cannot  be  directly  observed  and  pursued.  We  can  say 
nothing  more  definite  about  it  than  that  it  is  the  cause  of 
motion.  But  we  can  prove  that  motion  is  never  annihilated, 
for  whenever  motion  ceases,  its  cessation  is  only  apparent. 
The  movement  of  masses  of  matter,  visible  to  us,  has  either 
changed  into  a  movement  of  the  smallest  particles  of  matter, 
of  the  atoms,  or  into  '  latent  motion,'  into  so-called  ^  potential 
energy,'  from  which,  at  any  time  under  appropriate  conditions, 
the  same  amount  of  motion  can  again  arise. 

If  a  stone  fall  to  the  ground  and  remain  lying  there,  motion 
has  not  ceased.  The  place  on  the  ground  where  it  fell,  and 
the  stone  itself,  have  become  warmed,  and  heat  is  well  known 
to  be  a  mode  of  motion.  If  a  stone  is  thrown  straight  up  in 
the  air,  it  rises  with  decreasing  rapidity  and  comes  at  last  to 
rest.  At  that  moment  its  movement  is  latent,  and  is  stored 
up  in  it  as  potential  energy.  By  virtue  of  this  potential 
energy  it  now  comes  down  again,  and  reaches  the  ground  at 
the  same  velocity  with  which  its  ascent  began.  In  rising, 
the  energy  of  movement,  the  so-called  ^kinetic  energy,'  is 
converted  into  potential  energy ;  in  falling,  the  potential 
into  kinetic  energy.  The  conversion  of  kinetic  into  poten- 
tial energy  is  called  '  work,'  and  the  science  of  mechanics 
teaches  the  well-known  fact  that  work  is  measured  by  the 
product  of  the  weight  raised  into  the  height  to  which  it  is 
raised,  and  that  it  is  always  the  same  as  the  kinetic  energy, 

^  Physiology  cannot  be  studied  to  any  advantage  without  a  thorough  knowl- 
edge of  the  law  of  the  conservation  of  energy,  which  can  only  be  acquired  by 
advanced  mathematical  and  physical  studies.  This  lecture  may  serve  the  be- 
ginner, who  has  hitherto  neglected  these  subjects,  as  a  slight  preliminary  account. 

27 


28  LECTURE   III 

which  is  measured  by  the  product  of  half  the  mass  into  the 
square  of  the  velocity.  If  the  stone  that  is  thrown  up  be 
supported  at  the  moment  it  has  reached  the  highest  point  and 
comes  to  rest,  the  energy  can  remain  stored  up  in  it  for  an 
unlimited  period.  But  as  soon  as  the  support  is  removed, 
potential  is  again  converted  into  kinetic  energy ;  it  falls  with 
increasing  rapidity,  and  reaches  the  ground  at  the  same  speed 
with  which  its  ascent  began.  Hence  none  of  the  kinetic  energy 
has  been  lost.  If  it  strikes  the  ground,  an  amount  of  heat  is 
generated,  which  under  appropriate  conditions — for  instance, 
by  means  of  a  steam-engine — would  exactly  suffice  to  raise  the 
stone  to  the  same  height  from  which  it  fell.  Thus  no  energy 
is  lost  in  the  conversion  of  the  kinetic  energy  of  moving  masses 
into  the  kinetic  energy  of  moving  atoms,  and  vice  versa.  As  is 
well  known,  it  has  been  proved  by  numerous  experiments,  made 
by  different  observers  and  conducted  upon  various  methods,  that 
425  kilogrammeters  of  work  produce  one  unit  of  heat  (i.  e.,  the 
amount  of  heat  required  to  raise  the  temperature  of  one  kilo- 
gramme of  water  by  1°  C),  and  that  the  unit  of  heat  exactly 
suffices  to  accomplish  work  equal  to  425  kilogrammeters. 

Let  us  imagine  a  tube  to  be  laid  through  the  globe  and 
its  center  of  gravity,  from  us  to  our  antipodes,  and  let  us 
further  imagine  a  stone  brought  to  rest  in  this  tube,  so  that 
the  center  of  gravity  of  the  stone  coincides  with  the  center 
of  gravity  of  the  earth  ;  in  this  case  the  stone  would  remain 
motionless  and  free,  suspended  in  the  air.  But  if  the  stone,  by 
virtue  of  any  kinetic  energy,  were  raised  to  our  end  of  the  tube, 
a  reserve  of  potential  energy  would  now  be  stored  up  in  it,  by 
means  of  which  the  stone,  as  soon  as  it  is  left  to  itself,  returns 
with  increasing  rapidity  to  the  middle  of  the  tube.  At  the 
moment  when  its  center  of  gravity  coincides  with  that  of  the 
earth,  all  potential  energy  is  used  up  and  converted  into  kinetic 
energy,  and  has  attained  its  greatest  velocity.  This  kinetic 
energy  cannot  be  lost ;  it  drives  the  stone  further  on,  it  is  re- 
converted into  potential  energy,  work  is  accomplished,  the  stone 
is  driven  to  the  other  end  of  the  tube,  to  the  antipodes.  By 
this  time  the  kinetic  energy  is  used  up,  and  is  contained  in  the 
stone  as  potential  energy,  by  means  of  which  the  stone  again 
falls  with  increasing  speed  to  the  earth's  center  of  gravity,  and 
rises  with  diminishing  velocity  to  us.  And  if  the  tube  be  free 
from  air,  the  stone  must  thus  swing  backwards  and  forwards  to 
all  eternity,  none  of  its  movement  being  lost.  But  if  there  is 
air  in  the  tube,  a  part  of  the  kinetic  energy  of  the  stone  will 
be  continually  given  over  to  the  individual  molecules  of  air  ; 
the  stone  will    swing  backwards    and    forwards  at  constantly 


CONSERVATION    OF    ENERGY  29 

decreasing  dfstances  from  the  center  of  gravity,  where  it  finally 
comes  to  rest.  At  this  moment,  the  whole  kinetic  energy  of 
the  stone's  moving  bulk  is  converted  into  the  kinetic  energy  of 
moving  molecules,  which  we  call  heat.  But  nothing  is  lost ; 
precisely  as  many  units  of  heat  are  produced  as  correspond 
to  the  kilogrammeters  of  work  performed  by  the  rise  of  the 
stone  from  the  earth's  center  of  gravity  to  the  end  of  the 
tube. 

The  same  principle  seen  in  this  imaginary  and  impracticable 
experiment  may  be  observed,  only  in  a  more  complicated  form, 
in  every  swinging  pendulum.  The  pendulum  would  also 
oscillate  to  all  eternity,  if  the  kinetic  energy  of  the  moving 
mass  were  not  converted  into  heat  by  the  friction  at  the  point 
of  attachment  and  with  the  air. 

If  we  make  use  of  that  form  of  kinetic  energy  which  we 
call  the  electric  current,  to  split  up  a  chemical  compound  (for 
instance,  to  resolve  water  into  its  elements,  hydrogen  and 
oxygen),  a  part  of  the  kinetic  energy  disappears,  but  only 
apparently  so ;  it  is  converted  into  that  form  of  latent  move- 
ment which  we  term  chemical  potential  energy,  and  which  is 
entirely  analogous  to  the  force  with  which  the  stone  falls  when 
raised.  Chemical  potential  energy  is  stored  up  in  the  sepa- 
rate atoms.  If  they  again  unite,  the  potential  energy  they 
contain  is  again  converted  into  kinetic  energy,  which  appears 
to  us  as  light  and  heat ;  as,  for  instance,  when  a  flame  is 
produced  by  the  combination  of  oxygen  and  hydrogen.  By 
means  of  a  thermopile,  the  heat  produced  might  be  reconverted 
into  electrical  movement,  which  would  be  found  exactly  equal 
to  the  amount  originally  required  to  split  up  the  water. 
Nothing  would  be  lost. 

We  thus  see  that  nature  possesses  a  certain  store  of  kinetic 
energy,  which  can  in  no  way  be  either  increased  or  diminished. 
If  one  part  of  matter  comes  to  rest,  another  part  is  set  in 
motion.  Movement  of  masses  is  converted  into  movement  of 
molecules,  molecular  movement  into  movement  of  masses ; 
kinetic  into  potential  energy,  and  potential  into  kinetic  energy. 
The  sum  total  of  all  potential  energy  and  of  all  kinetic  energy 
always  remains  the  same.  This  law  is  called  the  Law  of  the 
Conservation  of  Energy. 

All  movements  on  the  surface  of  the  earth  (with  the  single 
exception  of  the  tides,  which  are  connected  with  the  rotation 
of  the  earth  on  its  axis)  may  be  traced  back  to  one  common 
source,  to  the  sun's  rays  of  light  and  heat.  The  varying  degree 
of  heat  of  the  different  layers  in  air  and  water  is  the  cause  of 
all  currents  of  sea  and  air,  the  storms  and   winds.     Sailing; 


30  LECTURE    III 

vessels  and  windmills  are  moved  by  sunbeams.  By  using  up 
the  kinetic  energy  of  the  sun's  heat,  vapor  arises  from  the 
surface  of  water,  and  is  raised  to  the  higher  layers  of  the 
atmosphere.  If  the  vapor  is  condensed  in  the  colder  upper 
regions,  the  kinetic  energy  of  the  waves  of  ether  reappears  as 
the  kinetic  energy  of  the  falling  raindrops,  or,  when  the  rain- 
drops collect,  as  the  kinetic  energy  of  flowing  brooks  and  rivers. 
It  is  sunlight  that  reappears  in  the  sparks  from  the  millstone ; 
it  is  the  sun's  heat  which  issues  from  the  glowing  hammers  and 
saws,  wheels,  axles,  and  rollers  of  all  machiues  set  in  motion 
by  water. 

We  now  come  to  the  question  of  the  forms  of  energy  and 
motion  which  are  met  with  in  vital  processes.  We  have  seen 
that  the  plant  is  always  taking  up  carbonic  acid  and  water, 
separating  the  oxygen  from  these  compounds,  and  thereby 
forming  other  compounds  poorer  in  oxygen  and  with  a  great 
affinity  for  oxygen.  There  is  thus  a  large  reserve  of  chemical 
potential  energy  stored  up  in  the  plant.  By  combustion  of  the 
plant  by  reunion  of  its  constituents  with  oxygen,  we  can 
convert  this  potential  energy  into  heat,  and  the  heat,  by  means 
of  steam  engines,  into  mechanical  work.  Now,  what  is  the 
source  of  this  chemical  potential  energy  ?  It  cannot  have 
originated  from  nothing.  Energy  is  eternal.  But  no  potential 
energy  is  conveyed  to  the  plant  by  its  food.  Carbonic  acid 
and  water  are  fully  oxidized  compounds ;  they  cannot  produce 
movement,  any  more  than  the  stone  lying  on  the  ground.  Not 
till  the  stone  is  raised  by  the  employment  of  kinetic  energy, 
can  it  fall  down  ;  and  not  till  the  oxygen  is  separated  from  the 
carbon  and  hydrogen  in  the  plant  by  the  employment  of  kinetic 
energy,  can  chemical  potential  energy  arise  in  it,  to  be  con- 
verted into  light  and  heat  and  mechanical  work.  The  force 
which  effects  the  separation  of  the  oxygen  in  the  plant  is  again 
nothing  but  sunlight.  We  know  that  the  plant  liberates 
oxygen  only  so  long  as  sunshine  reaches  it,  and  that  the  amount 
of  oxygen  set  free  varies  in  proportion  to  the  intensity  of  the 
light.  This  maintenance  of  the  proportion  was  proved  by 
Wolkoff  ^  by  the  following  simple  experiment. 

Wolkoff  counted  the  gas-bubbles  which  arose  from  water- 
plants  when  the  rays  of  the  sun,  conducted  through  a  flat  piece 
of  ground  glass,  were  allowed  to  fall  upon  them.  The  water- 
plants  were  in  a  glass  vessel,  which  could  be  moved  to  any 
distance  from  the  light  as  required.  The  intensity  of  the  light 
is  well  known  to  be  in  inverse  proportion  to  the  square  of  the 
distance  from  the  point  of  light.  Wolkoif  found  that  the 
^  Al.  von  Wolkoff,  Jahrb.  f.  wissensch.  Botanik.,  vol.  v.  p.  1 :  1866. 


CONSERVATION    OF    ENERGY  31 

number  of  oxygen-bubbles  was  increased  and  diminished  in 
simple  proportion  to  the  intensity  of  the  light. 

Van  Tieghem  ^  obtained  the  same  result  when  he  tried  the 
experiment  with  artificial  light.  The  number  of  gas-bubbles 
from  the  water-plants  diminished  as  the  square  of  the  distance 
from  the  candle. 

Hence  there  can  be  no  doubt  that  all  the  potential 
energy  of  vegetable  substances  is  converted  sunlight.  It  is 
sunlight  that  reappears  in  the  fire  of  burning  wood.  It  is  sun- 
light that  gives  us  light  in  the  form  of  gas-jets  and  petroleum 
flames.  The  gaslight  which  at  this  moment  illuminates  us, 
has  shone  on  our  earth  before,  millions  and  millions  of  years 
ago ;  it  has  lain  dormant  in  our  earth  for  millions  of  years,  and 
reappears  again  at  this  moment.  The  whole  immense  store  of 
energy  which  lies  in  the  vast  coal  strata,  which  sets  all  machines 
and  locomotives  in  motion,  is  only  the  fixed  kinetic  energy  of 
sunlight  which  was  once  shining  upon  the  luxuriant  vegetation 
of  the  prehistoric  world. 

The  substances  formed  by  plants  serve  as  food  for  animals. 
The  oxygen  which  is  liberated  from  the  water  and  carbonic 
acid  in  the  plant  by  the  kinetic  energy  of  sunlight,  is  in  the 
animal  body  again  united  with  compounds  that  are  deficient  in 
oxygen,  and  the  ultimate  products  of  this  combination  are 
again  given  off  as  carbonic  acid  and  water,  the  same  simple 
substances  which  serve  the  plant  as  food.  The  chemical 
potential  energy  of  food  is  thus  used  up.  But,  as  no  energy 
can  perish,  we  must  expect  to  find  an  equivalent  amount  of 
other  forms  of  energy  appearing  in  the  animal  body.  And 
indeed  we  know  that,  firstly,  all  animals  have  a  temperature 
higher  than  that  of  their  surroundings,  that  they  are  thus  con- 
tinually producing  heat;  and  that,  secondly,  they  carry  out 
movements,  or  perform  work. 

The  sum  of  the  work  executed  by  an  animal,  and  of  the 
heat  which  it  gives  out,  must  therefore  be  exactly  equivalent 
to  the  chemical  potential  energy  taken  in  with  its  food,  and 
to  the  kinetic  energy  of  sunlight  used  up  in  the  production  of 
this  potential  energy  in  the  plant. 

The  difficulties  of  obtaining  precise  experimental  proof  of 
this  equivalence  are  very  great.  So  far  as  the  precision 
hitherto  attained  allows  us  to  judge,  direct  experiments  prove 
that  such  equivalence  does  exist :  that  the  amount  of  heat  and 
work  produced  by  an  animal,  expressed  in  units  of  heat,  is 
equal  to  the  amount  of  heat  generated  by  the  food-stuff  of  the 
animal  when  burnt  outside  the  organism. 

^  Van  Tieghem,  Compt.  rend.,  vol.  Ixix.  p.  482  :  1869. 


32  LECTURE    III 

The  first  experiment  of  this  kind  was  carried  out  by 
Lavoisier  ^  as  early  as  the  year  1780.  The  object  was  to  prove 
that  combustion  is  the  sole  source  of  animal  heat.  A  guinea- 
pig  was  placed  in  an  ice-calorimeter,  and  the  quantity  of  water 
produced  in  ten  hours  by  the  melting  of  the  ice  was  measured. 
It  amounted  to  341.08  grms.  The  same  guinea-pig  was  then 
put  under  a  bell-jar  over  mercury.  A  current  of  air  was 
passed  through  the  bell-jar  and  then  conducted  through  caustic 
potash,  which  retained  the  carbonic  acid.  The  amount  of-  the 
latter  was  quantitatively  determined.  The  mean  of  several  ex- 
periments showed  that  the  guinea-pig  in  ten  hours  gave  out 
3.333  grms.  of  carbon  in  the  form  of  carbonic  acid.  Lavoisier 
and  Laplace  had  previously,  by  means  of  the  calorimeter, 
determined  the  heat  of  combustion  of  carbon,  and  found  that 
the  heat  produced  by  the  combustion  of  3.333  grms.  of  carbon 
melted  326.75  grms.  of  ice.  Were  Lavoisier's  hypothesis,  that 
animal-heat  arises  from  the  combustion  of  the  carbon  in  the 
food-stuffs,  correct,  the  amount  of  heat  or  of  ice-water  found  in 
the  above  experiment  on  an  animal  would  necessarily  be  pre- 
cisely as  great  as  in  the  combustion  of  the  carbon,  provided 
the  production  of  carbonic  acid  were  the  same  in  both  instances. 
As  a  matter  of  fact,  it  was  found  thus — 

326^  _ 
341:Ö8~^'^^- 

It  was  a  mere  chance  that  the  numbers  approximated  each 
other  so  closely.  Any  one  with  our  present  knowledge,  who 
criticised  the  experiment,  would  easily  discover  numerous 
sources  of  error.  Indeed  its  chief  defects  did  not  escape 
Lavoisier's  penetration.  He  had  already  discovered  that  the 
whole  of  the  oxygen  inspired  did  not  reappear  in  the  carbonic 
acid  exhaled,  and  he  therefore  assumed  that  the  oxygen  which 
had  disappeared  went  to  form  water.  Lavoisier  had  further 
observed  that  the  temperature  of  the  animal  in  the  calorimeter 
was  lower  at  the  conclusion  of  the  experiment  than  at  the 
commencement ;  that  the  animal  therefore,  during  the  progress 
of  the  experiment,  partially  lost  its  heat,  which  arose  from 
combustion  that  took  place  before  the  experiment  began,  and 
which  did  not  therefore  correspond  to  the  amount  of  carbonic 
acid  exhaled  during  the  experiment.  For  both  reasons,  the 
quantity  of  water  produced  in  the  calorimeter  must  be  greater 
than  what  would  correspond  to  the  carbonic  acid  produced. 
The  necessity  for  a  more  exact  repetition  of  Lavoisier's 

^  Lavoisier  et  de  la  Place,  Memoircs  de  I' Acad,  royale  des  Sciences,  p.  355 : 
1780. 


CONSERVATION    OF    ENERGY  33 

experiments  'was  soon  afterwards  recognized  by  the  French 
Academy  ;  and  in  1822  they  offered  a  prize  on  the  subject 
of  the  source  of  animal  heat.  There  were  two  competitors, 
Despretz  and  Dulong.  The  prize  was  awarded  to  Despretz 
and  his  work  appeared  in  the  year  1824.^  Dulong's  work, 
which  was  carried  out  on  the  same  principle,  was  not  printed 
till  after  his  death.^ 

Both  experimenters  made  use  of  a  water-calorimeter.  The 
animal  being  in  the  calorimeter,  atmospheric  air  was  passed 
from  one  gasometer  through  the  air  chamber  immediately 
around  the  animal,  and  collected  in  another  gasometer.  In 
this  way  the  quantity  of  the  oxygen  used  up,  and  carbonic 
acid  formed,  was  determined.  The  latter  did  not  correspond 
to  all  the  oxygen  consumed  ;  the  excess  of  oxygen  was  sup- 
posed to  have  united  with  hydrogen  to  form  water.  The  heat 
of  combustion  of  hydrogen  and  carbon  was  calculated  from 
the  figures  given  by  Lavoisier  and  Laplace.  The  amount  of 
heat  estimated  in  this  way  was  compared  with  the  amount 
of  heat  produced  in  the  calorimeter.  Both  Despretz  and 
Dulong  found  the  amount  of  the  former  smaller  than  of  the 
latter.  In  the  experiments  of  Dulong,  the  number  calculated 
amounted  from  68.8  to  83.3  per  cent,  of  the  number  found ;  in 
those  of  Despretz,  from  74.0  to  90.4  per  cent. 

Among  the  numerous  sources  of  error  in  this  calculation, 
the  following  may  be  specially  noticed  :  1.  The  numbers  given 
by  Lavoisier  and  Laplace,  which  form  the  basis  of  the  com- 
parison, are,  as  subsequent  and  more  exact  investigation  has 
shown,  too  low.  2.  The  heat  of  combustion  of  the  food-stuffs 
is  not  equivalent  to  that  of  their  component  elements,  but  a 
little  less,  since  a  certain  amount  of  kinetic  energy  is  used  up 
in  effecting  their  dissociation.  3.  The  quantity  of  carbonic  acid 
in  the  expired  air  must  be  too  small,  since  the  gas  in  the  gaso- 
meter was  confined  over  water,  which  would  absorb  some  of 
the  carbonic  acid.  4.  The  time  occupied  by  the  experiment 
was  much  too  short ;  it  was  only  two  hours.  The  processes  of 
combustion  and  the  taking  up  of  oxygen  or  elimination  of 
carbonic  acid  are  not  proportional  in  every  short  interval ;  only 
during  longer  periods  is  there  an  approximate  correspondence. 
The  quantities  of  oxygen  and  carbonic  acid,  and  of  the  inter- 
mediate products  of  combustion  contained  in  the  tissues  of  the 
body,  vary  greatly  at  different  times. 

1  Despretz,  "  Recherches  experimentales  sur  les  causes  de  la  chaleur  ani- 
male":  Paris,  1824  ;  also  Ann.  de  chim.  et  dephys.,  vol.  xxvi.  p.  337  :  1824. 

2  Dulong,"  Memoire  sur  la  chaleur animale,"  Ann.  de  chim.  et  dephys.,  ser. 
iii.  vol.  i.  p.  440:  1841.  See  also  "  Recherches  sur  la  chaleur,  trouvees  dans  les 
papiers  de  M.  Dulong,"  Ann.  de  chim.  et  de  phys.,  ser.  iii.  vol.  viii.  p.  180 :  1843. 

3 


34  LECTURE    III 

At  a  later  period  Gavarret  ^  calculated  the  numbers  obtained 
by  Dulong  and  Despretz,  and,  by  correcting  certain  errors, 
found  the  values  84.7  to  101.8  per  cent.,  as  a  mean  92.3  per 
cent.;  instead  of  the  proportion  of  74.0  to  90.4  per  cent.,  as 
found  by  Dulong  and  Despretz. 

The  movements  of  the  animal  while  confined  in  the  calori- 
meter must  have  been  almost  entirely  converted  into  heat "  and 
observed  as  such ;  they  must  have  produced  heat  by  the  mutual 
friction  of  the  parts  moved,  by  the  rubbing  of  the  animal 
against  the  walls  of  its  cage,  and  by  the  shaking  of  the  water 
in  the  calorimeter  thus  set  up. 

In  recent  years  M.  Rubner  ^  has  taken  up  the  same  subject 
with  all  the  aids  afforded  by  modern  apparatus  and  technique, 
and  has  succeeded  in  demonstrating  the  exact  equivalents  be- 
tween the  chemical  potential  energy  taken  up  by  the  body  in 
the  form  of  food  and  the  kinetic  energy  given  out  by  the 
animal.  In  Rubner's  experiments  on  dogs  these  amounts,  as  a 
matter  of  fact,  differed  only  by  about  |^  to  1|^  per  cent. 

We  thus  see  that  the  law  of  the  conservation  of  energy  rules 
in  the  department  of  animal  life.  The  body-heat,  our  move- 
ments, all  our  vital  functions — so  far  as  they  are  perceptible  to 
our  senses — are  transmuted  sunlight. 

We  may  now  inquire  into  the  relation  borne  by  our  psychical 
processes  to  the  conservation  of  energy.  Are  all  our  feelings, 
emotions,  instincts,  ideas  only  converted  sunlight,  or  must  we 
assume  that  the  world  of  the  internal  sense  does  not  obey  the 
great  uniform  law  to  which  the  whole  world  of  the  external 
senses  yields  constant  and  unwavering  allegiance  ? 

It  is  beyond  doubt  that  there  is  a  certain  causal  connection 
between  psychical  processes  and  certain  material  modes  of  motion 
in  our  bodies.  Sensation  is  excited  by  a  process  of  movement  in 
the  nervous  system.  A  muscular  contraction  is  the  result  of  an 
impulse  of  the  will.  But  the  question  arises  as  to  the  nature  of 
this  causal  connection.  Is  it  really  a  causal  connection  of  the 
same  kind  as  the  law  of  the  conservation  of  energy  demands, 
that  proportion  should  exist  between  cause  and  effect?  Or 
have  we  to  deal  with  other  kinds  of  causal  connection  ? 

Above  all  things,  we  must  sharply  distinguish  between  an 
immediate  cause  and  an  ultimate  cause,  a  distinction  so  neces- 
sary for  the  comprehension  of  physiological  processes  that  I 
may  be  permitted  to  give  one  or  two  illustrations.  It  is  usual 
to  define  the  cutting  through  of  a  string  by  which  a  weight  is 
held  up  as  the  cause  of  falling.     But   the  real  cause   is  the 

'  Gavarret,  "  De  la  chaleur  produite  par  les  etres  vivants  ":  1855. 
^M.  Rubner,  Zeitschr.  f.  Biol.,  vol.  xxx.  p.  73:  1894. 


CONSEEVATION    OF    ENEEQY  35 

work  which  has  been  performed  in  raising  the  weight.  This  is 
proportional  to  the  kinetic  energy  of  the  falling  weight.  If 
the  lifting  is  efPected  by  muscular  force,  the  latter  owes  its 
origin  to  the  chemical  potential  energy  of  food,  which  was 
originally  derived  from  the  kinetic  energy  of  sunlight  in 
the  plant.  If  the  falling  weight  strikes  the  ground,  the 
energy  of  sunlight  again  makes  its  appearance  as  heat. 
All  these  forces,  the  kinetic  energy  of  the  sunlight,  the 
chemical  potential  energy  of  food,  the  kinetic  energy  of 
muscular  movement,  the  potential  energy  of  the  lifted  weight, 
the  heat  produced  by  the  falling  weight,  &c.,  are  related  as 
cause  and  effect ;  they  are  proportional  and  equivalent — the 
same  thing  appearing  in  different  shapes.  The  effect  is  the 
cause  itself  in  a  changed  form.  Cutting  the  string  is  only  the 
immediate  or  exciting  cause,  the  impetus  which  starts  the  con- 
version of  cause  into  effect,  of  potential  into  kinetic  energy. 
Between  the  exciting  cause  or  '  liberating  force,'  as  it  is  also 
called,  and  the  effect,  there  is  no  sort  of  proportion.  The 
weight  may  be  hung  up  by  a  string  and  the  latter  cut  through 
with  a  razor,  or  the  same  weight  may  be  hung  up  by  a  rope 
and  the  latter  shot  through  by  a  cannon-ball — the  kinetic 
energy  of  the  falling  stone  remains  the  same. 

The  movement  of  a  locomotive  is  transmuted  heat ;  the 
heat  is  produced  by  chemical  potential  energy,  by  the  affinity 
of  the  fuel  for  oxygen  ;  the  chemical  potential  energy  is  the 
converted  energy  of  sunlight.  The  kinetic  energy  of  the 
moving  engine  is  completely  used  up  in  overcoming  friction. 
The  heat  which  causes  the  movement  of  the  locomotive  appears 
again  in  the  heated  rails,  wheels,  and  axles.  It  is  the  same 
heat  which,  as  the  heat  of  the  sun,  produced  the  chemical 
potential  energy  in  the  plant.  The  energy  of  the  sunlight,  the 
potential  energy  of  the  fuel,  the  heat  of  the  furnace,  the  kinetic 
energy  of  the  engine,  the  heat  produced  by  friction,  are  all 
proportional  and  equivalent ;  they  are  identical.  The  flame, 
which  was  used  to  light  the  fire  in  the  furnace,  is  merely  the 
exciting  cause  of  the  conversion  of  chemical  energy  into  heat ; 
the  amount  of  heat  produced  is  totally  independent  of  it.  A 
single  lucifer  match  may  set  fire  to  one  pound  or  a  thousand 
pounds  of  wood,  or  even  to  a  whole  forest ;  but  the  heat  pro- 
duced is  in  proportion  to  the  amount  of  chemical  energy  used 
up,  and  is  entirely  independent  of  the  liberating  force. 

In  the  case  of  a  rifle,  the  pulling  of  the  trigger  constitutes 
the  liberating  force  for  converting  the  potential  energy  of  the 
spring  into  the  kinetic  energy  of  the  falling  hammer.  The 
energy  of  the  hammer  is  converted  into  molecular  movement, 


36  LECTURE   III 

which  again  acts  as  a  liberating  force  in  causing  the  explosion 
of  the  percussion-cap ;  this  explosion  acts  as  the  exciting  cause 
for  the  conversion  of  the  chemical  potential  energy  of  the 
powder  into  the  kinetic  energy  of  the  ball. 

In  addition  to  the  ultimate  cause,  and  the  exciting  cause,  a 
third  factor  is  generally  required  in  the  production  of  a  definite 
result,  which  I  will  call  the  determining  factor.  In  the  last 
illustration,  the  determining  factor  for  the  projection  of  the 
bullet  is  to  be  found  in  the  fact  that  the  latter  is  contained  in 
the  barrel  of  the  rifle,  and  thus  only  able  to  pass  in  one  direction. 
For  the  production  of  a  definite  movement,  a  certain  arrange- 
ment of  surrounding  objects  is  a  necessary  determining  factor. 
We  can  thus  distinguish  between  three  sorts  of  causes :  the 
ultimate  cause,  the  exciting  cause,  and  the  determining  cause. 

It  must  be  observed  that  in  certain  exceptional  cases 
there  is  a  proportion  between  the  effect  and  the  exciting 
cause.  A  well-known  instance  of  this  is  seen  in  the  drawing 
up  of  a  sluice.  The  work  performed  in  raising  it  is  in  pro- 
portion to  the  cross  section  of  the  falling  current  of  water,  and 
to  the  kinetic  energy  of  the  water.  Nevertheless,  the  drawing 
up  of  the  sluice  is  only  the  exciting  cause  which  converts  the 
potential  energy  of  the  dammed  up  water  into  the  kinetic 
energy  of  water  in  motion. 

Similarly,  if  we  have  a  number  of  weights  hung  up  by 
strings  of  uniform  size,  the  work  done  in  cutting  through  the 
strings  will  be  in  proportion  to  their  number,  and  consequently 
in  proportion  to  the  kinetic  energy  of  the  falling  weights. 
And  yet  the  cutting  is  only  the  exciting  cause. 

We  may  now  return  to  the  question  as  to  the  relation 
between  psychical  and  physical  processes. 

The  impulse  of  the  will  and  muscular  contraction  certainly 
do  not  stand  to  each  other  in  the  relation  of  cause  and  effect  in 
the  limited  sense.  The  impulse  of  the  will  is  merely  the 
exciting  cause.  The  ultimate  cause  is  the  chemical  potential 
energy  of  the  food  which  is  used  up  in  the  muscle,  and  is 
therefore  converted  sunlight.  But  the  impulse  of  the  will 
does  not  even  afford  the  direct  impetus  for  the  conversion  of 
chemical  energy  into  the  kinetic  energy  of  muscle.  There  is 
probably  a  long  chain  of  causes,  such  as  processes  in  the  brain, 
nervous  system,  and  muscle,  analogous  to  those  shown  to  exist 
in  the  illustration  of  the  rifle. 

The  question  as  to  the  nature  of  the  causal  connection  be- 
tween stimulation  of  the  senses  and  the  sensations  themselves, 
is  much  more  difiicult  to  decide.  Here  there  is  undoubtedly 
quantitative   proportion.     The   intensity  of  the  sensation    in- 


CONSERVATION    OF    ENERGY  37 

creases  with  the  strength  of  the  stimulation ;  but  is  there  any- 
proportionate  relation  between  the  two  ? 

We  shall  not  be  able  to  decide  this  question,  so  long  as  we 
possess  no  means  of  measuring  the  intensity  of  sensations,  or  of 
any  other  psychical  conditions  and  processes  ;  in  the  present 
state  of  human  knowledge  and  of  human  intellect,  it  appears 
quite  inconceivable  that  such  means  should  ever  be  discovered.^ 
We  are  therefore  unable  to  answer  the  question  whether  the 
phenomena  of  consciousness  follow  the  law  of  the  conservation 
of  energy,  and  whether  they  are  transmuted  sunlight, 

I  must  note  that  there  is  probably,  in  the  afferent  and 
central  organs,  a  chain  of  processes  intervening  between 
stimulation  and  sensations,  as  there  is  between  will  and 
muscular  action.  We  are  quite  unable  to  decide  whether 
the  last  form  of  motion,  which  reaches  the  brain  as  the  result 
of  stimulation,  is  converted  into  sensation,  or  only  serves  as  an 
impulse  originating  sensation,  possibly  from  chemical  potential 
energy.  It  is  conceivable  that  an  entirely  new  and  particular 
kind  of  causal  connection  may  be  at  work  in  this  case. 

The  theory  has  nevertheless  often  been  advanced  that 
there  is  an  exhaustion  of  chemical  potential  energy,  of  food- 
substances,  corresponding  to  the  performance  of  psychical 
functions.  People  have  even  tried  to  prove  experimentally 
that  intellectual  exertion  has  an  influence  on  metabolism,  as 
shown  by  the  amount  of  excretions.  All  these  experiments 
fail  on  account  of  the  impossibility  of  measuring  intellectual 
exertion,  of  even  deciding  whether  it  was  greater  or  less.  A 
man  who  shuts  himself  up  in  a  dark  room,  with  the  intention 
of  keeping  his  mind  a  blank,  may  involuntarily  exercise  it  more 
than  if  he  were  to  sit  down  to  his  books  with  the  intention  of 
exerting  all  his  intellectual  faculties  ;  besides,  we  ought  to  take 
into  consideration  the  emotions,  which  probably  far  exceed  all 
mental  exertions  in  the  expenditure  of  energy,  and  which  we 
cannot  call  into  play  or  dismiss  at  will. 

We  must  consider  moreover  that  the  weight  of  the  brain 
is  less  than  2  per  cent,  of  the  weight  of  the  body,  and  that 
only  a  portion  of  the  brain  is  employed  in  mental  functions. 
Even  if  the  metabolism  of  this  organ  were,  by  higher  psychical 

^  Fechner  ("  Elemente  der  Psychophysik  "  :  Leipzig,  1860),  taking  Weber's 
law  as  his  starting-point  (viz.,  that  the  increase  of  stimulation  must  grow  in 
proportion  to  the  stimulation  already  existing,  in  order  to  produce  a  minimal 
increase  in  sensation),  arrives  at  the  conclusion  that  sensations  are  proportionate 
to  the  logarithm  of  the  stimuli.  Attention  has  frequently  been  drawn  to  the 
fact  that  the  assumed  equality  of  the  minimal  increments  of  sensation,  upon 
which  the  computation  is  founded,  is  purely  arbitrary.  This  is  not  the  place  to 
enter  more  fully  into  this  subject. 


38  LECTimE  III 

activity,  promoted  to  the  utmost,  we  could  not  expect  to  recog- 
nize this  fact  in  an  increase  of  the  total  metabolism.  Even  if 
it  could  be  distinguished,  we  should  not  be  justified  in  conclud- 
ing that  the  work  of  the  mind  was  converted  potential  energy. 
The  connection  might  be  an  indirect  one. 

With  a  knowledge  of  this  point  of  view,  the  beginner  will 
be  in  a  position  to  peruse  critically  the  works  ^  that  have 
appeared  concerning  the  influence  of  mental  work  on  meta- 
bolism. 

In  recapitulating  the  main  features  of  our  previous  remarks 
the  following  contrasts  strike  us  in  the  changes  that  animal 
and  vegetable  substances  undergo  : — 

1.  The  plant  forms  organic  substances  ;  the  animal  destroys 
organic  substances.  The  vital  process  in  the  plant  is  synthetic, 
in  the  animal  anahi:ic. 

2.  The  life  of  the  plant  is  a  process  of  reduction  ;  the  life  of 
the  animal  a  process  of  oxidation. 

3.  The  plant  uses  up  kinetic  energy  and  produces  potential 
energy ;  the  animal  uses  up  potential  energy  and  produces 
kinetic  energy. 

But  "  nature  takes  no  leaps."  In  morphology  no  definite 
demarcation  can  be  dra^vn  between  plants  and  animals ;  in  the 
same  way  the  contrast  between  them  disappears  when  we 
examine  the  two  kingdoms  in  relation  to  the  conversion  of 
energy  and  metabolic  processes  which  they  exhibit. 

There  are  unicellular  beings  without  chlorophyl,  such  as 
fungi  and  bacteria,  which  are  incapable  of  assimilating  the 
carbon  of  carbonic  acid.  It  must  be  brought  to  them  as  an 
organic  compound,  as  sugar,  tartaric  acid,  &c.  Here  they 
resemble  animals.  But  they  can  assimilate  nitrogen  in  inor- 
ganic compounds,  as  ammonia  and  nitric  acid ;  here  they 
resemble  plants.  The  fungi  and  bacteria,  which  cause  fermen- 
tation and  processes  of  decomposition  (see  Lecture  XL),  use  up 
chemical  potential  energy  and  develop  kinetic  energy,  heat, 
and  movement  ;  again  behaving  like  animals.  But  by  synthesis 
they  form  proteid  from  ammonia  and  sugar,  thus  again  behav- 
ing like  plants.  In  our  future  observations  we  shall  see  that 
in  every  cell,  even  of  the  most  highly  organized  animal,  synthetic 
processes  occur  side  by  side  with  processes  of  decomposition,  as 
they  do  in  the  cells  of  plants.  Within  the  rigid  cellulose-wall 
of  every  vegetable  cell  is  a  contractile  protoplasmic  body  which 

^  Bcecker,  Beitr.  z.  Heilkutidt:  1849 ;  Hammond,  Amer.  Journal  of  3Iedical 
Sciences,  p.  330:  1856;  Sam.  Haughton,  Dublin  Quarterly  Journal  of  3Iedical 
Science,  p.  1 :  1860;  J.  W.  Paton,  Journal  of  Anatomy  and  Physiol.,  vol.  v.  p. 
296 :  1871 ;  Liebermeister,  Uandb.  d.  Pathol,  u.  Therap.  des  Fiebers,  p.  196  : 
Leipzig,  1875  ;  Speck,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xv.  p.  81 :  1882. 


CONSERVATION    OF    ENERGY  39 

breathes  and  performs  '  active '  movements  like  every  animal. 
In  every  part  of  a  plant  oxygen  is  used  up  and  carbonic  acid 
produced,  as  in  every  animal;  only  that,  in  the  parts  of  the 
plant  which  have  chlorophyl,  this  process  of  oxidation  is  hidden 
by  the  more  powerful  process  of  reduction.  But  even  this  only 
takes  place  so  long  as  sunlight  shines  upon  those  particular 
parts.  In  the  dark,  the  parts  of  the  plant  containing  chloro- 
phyl breathe  like  animals ;  the  parts  without  chlorophyl  do 
so  iu  the  sunlight  as  well. 

The  contrast  disappears  however  still  more  completely 
in  certain  highly  organized  phanerogams,  so-called  parasites, 
which  do  not  possess  chlorophyl,  and  which  derive  their 
nourishment  from  the  organic  substances  formed  by  other 
plants.  The  Monotropa,  for  instance,  is  in  morphological 
structure  a  Pyrolacea,  but  in  its  metabolism  it  is  an  animal. 

On  the  other  hand,  there  are  animals  which  contain 
chlorophyl.  Certain  worms  (Planarise)  and  Celenteratse  [Hydra 
viridis)  have  chlorophyl-granules,  seek  sunlight,  and  give  off 
oxygen  in  the  light,  but  soon  die  if  kept  in  the  dark.^  It  has 
however  been  more  recently  shown  by  Geza  Entz^  and  Karl 
Brandt  ^  that  the  chlorophyl-granules  are  not  free  in  the  tissues 
of  the  above-mentioned  animals,  but  are  enclosed  in  unicellular 
algse,  which  live  in  these  animals  as  '  symbionta.'  *  But  the 
chlorophyl-granules  in  plants  may  be  likewise  only  symbionta. 
So  far  it  is  certain  that  they  never  arise  in  the  tissues  of  plants 
in  any  other  way  than  by  division  of  other  chlorophyl-granules 
already   there.^      Besides   this.    Engelmann  ^   has    shown    that 

^  P.  Geddes,  Compt.  rend.,  vol.  Ixxxvii.  p.  1095:  1878;  and  Proc.  Roy.  Soc, 
vol.  xxviii.  p.  449  :  1879. 

2  Geza  Entz,  Ueber  die  Natur  der  '  Chlorophyllkörperchen  '  niederer  Thiere, 
Biolog.  Centralblatt,  vol.  i.  No.  21,  p.  646 :  January  20,  1882. 

^  Karl  Brandt,  Verh.  d.  physiol.  Gesellsch.:  Berlin,  November  11,  1881  ; 
Biolog.  Centralblatt,  vol.  i.  No.  17,  p.  524;  Arch.  f.  Änat.  ii.  Physiol.,  p.  125  : 
1882  ;  Mittheilungen  a.  d.  zoolog.  Station  zu  Neapel.,  vol.  iv.  p.  191 :  1883. 

^  The  term .'  symbionta '  is  applied  to  those  parasites  which  do  no  harm  to 
their  hosts,  each  being  of  mutual  assistance  to  the  other.  A  known  instance  of 
symbiosis  occurs  in  the  relationship  between  algse  and  fungi  in  the  thallus  of 
herpes  (Flechtea  thallus),  discovered  by  Schwendener  (Nägeli's  Beitr.  z.  wissensch. 
Bot.,  Heft  ii.,  iii.,  and  iv.:  Leipzig,  1860-68).  The  more  recent  discovery  of 
numerous  examples  of  symbiosis  is  undoubtedly  an  acquisition  of  the  greatest 
importance  in  every  branch  of  physiology.  The  name  "  Symbiosis  "  was  intro- 
duced by  De  Bary,  "Die  Erscheinung  der  Symbiose,"  Vortrag,  Strasbourg: 
Trübner,  1879.  An  interesting  account  of  the  literature  of  this  subject  will  be 
found  in  O.  Hertwig's  "  Die  Symbiose  oder  das  Genossenschaftsleben  im  Thier- 
reich,"  Vortrag:  Jena,  1883. 

5 Arthur  Meyer,  "Das  Chlorophyllkorn,"  p.  55:  Leipzig,  1883;  A.  F.  W. 
Schimper,  Jahrbücher  für  wissensch.  Botanik,  vol.  vi.  p.  188 :  1885.  An  account 
of  the  earlier  literatui'e  of  the  subject  will  be  found  here. 

=  Th.  W.  Engelmann,  Pfliiger's  Arch.,  vol.  xxxii.  p.  80:  1883.  The  method 
employed  by  Engelmann  to  prove  the  occurrence  of  oxygen  was  peculiar.    It  was 


40  LECTURE    III 

certain  infusoria,  Vorticellse,  contain  chlorophyl  diffused  in 
their  plasma,  which  likewise  gives  off  oxygen  in  sunshine. 

It  follows  that  a  complete  antithesis  between  interchange  of 
force  and  matter  in  animals  and  plants  does  not  exist ;  ^  and 
it  will  be  henceforward  impossible  to  separate  the  physiological 
chemistry  of  the  vegetable  from  that  of  the  animal  world.  The 
more  our  knowledge  of  each  section  of  science  advances,  the 
more  the  two  become  fused  together. 

based  on  the  fact  that  certain  bacteria,  eager  for  oxygen,  swarm  round  the  cells 
containing  chlorophyl.  Compare  the  earlier  and  highly  interesting  treatises  of 
Engelmann  in  Pfliiger's  Arch.,  vol.  xxv.  p.  285  :  1881 ;  vol.  xxvi.  p.  537  :  1881 ; 
vol.  xxvii.  p.  485  :  1882 ;  and  vol.  xxx.  p.  95 :  1883. 

^  Comp.  CI.  Bernard,  "  Lecons  sur  les  phenomenes  de  la  vie,  communs  aux 
animaux  et  aux  vegetaux  ":  Paris,  1878. 


LECTURE  IV 


THE     FOOD     OF     MAN DEFINITION    AND     CLASSIFICATION     OF 

FOOD-STUFFS THE    ORGANIC    FOOD-STUFFS PROTEID 

AND   GELATIN 

Our  observations  up  to  this  point  have  shown  us  that  the 
constituents  of  our  body  are  subject  to  a  constant  circulation, 
to  uninterrupted  change.  The  materials,  which  we  take  into 
our  body  to  replace  the  loss  which  is  always  going  on  in  this 
circulation,  are  called  food-stuifs.  This  is  the  definition  of  the 
term  food-stuifs  which  is  still  met  with  in  most  text-books. 
But  this  definition  is  incomplete ;  it  does  not  cover  the  whole 
meaning  of  food-stuffs ;  it  dates  from  the  time  before  the  law 
of  the  conservation  of  energy  was  discovered.  According  to 
this  definition,  water  would  be  the  most  important  food-stuff, 
for  our  body  contains  63  per  cent,  of  water,  which  is  constantly 
being  given  off  by  the  lungs,  the  skin,  and  the  kidneys ;  and 
this  loss  can  only  be  replaced  by  the  introduction  of  a  fresh 
supply.  The  rudest  form  of  empiricism,  untutored  common 
sense,  is  opposed  to  this  interpretation,  as  no  one  would  think 
of  calling  water  '  nutritious.'  Now,  why  is  water  not  nutritious  ? 
For  the  simple  reason  that  no  potential  energy  is  conveyed  to 
the  body  by  water.  Water  is  a  saturated  compound  ;  it  as 
little  produces  movement  as  a  stone  lying  on  the  ground.  The 
stone  cannot  fall  till  it  has  been  raised  from  the  ground  by  the 
employment  of  kinetic  energy ;  and  not  until  the  atoms  of 
oxygen  have  been  separated  from  the  atoms  of  hydrogen  and 
carbon  by  the  kinetic  energy  of  sunlight,  is  the  plant  enabled 
to  store  up  that  potential  energy  which  gives  rise  to  all  the 
forms  of  kinetic  energy  contributing  to  animal  life. 

We  shall  therefore  include  under  the  term  '  food-stuffs ' 
those  substances,  which  are  a  source  of  energy  in  the  body,  as 
well  as  those  which  replace  the  lost  constituents  of  the  body. 
There  are  substances  in  our  food  which  never  become  integral 
constituents  of  our  tissues,  but  which  go  to  form  a  source  of 
kinetic  energy.     To  these  belong  the  organic  acids  so  widely 

41 


42  LECTUEE    IV 

diffused  in  vegetable  food,  such  as  tartaric  acid,  citric  acid,  and 
malic  acid,  which  are  never  concerned  in  the  formation  of  the 
tissues,  but  are  burnt  up  to  form  carbonic  acid  and  water,  with 
the  liberation  of  kinetic  energy,  which  could  be  utilized  for  the 
performance  of  normal  functions.  To  these  we  may  perhaps 
add  the  carbohydrates,  which  likewise  do  not  appear  to  be 
employed  in  the  building  up  of  tissues,  although  we  know  for 
a  fact  that  they  are  the  principal  source  of  muscular  work. 
Hence  they  are  always  circulating  through  all  the  organs  of  the 
body  in  the  plasma  of  blood  and  lymph.  They  are  indeed 
also  found  deposited  in  the  tissues  in  the  form  of  glycogen,  but 
these  deposits  cannot  be  regarded  as  integral  constituents  of 
the  living  tissues ;  they  are  only  stores  of  potential  energy 
which  disappear  during  muscular  work  ;,  they  are  as  little  parts 
of  our  organism  as  coal  is  a  part  of  the  steam-engine.^  The 
gelatin-yielding  substances  in  our  food,  glutin,  chondrin,  ossein, 
likewise  serve  only  as  sources  of  energy,  and  never  assist  in 
repairing  the  waste  of  tissue.  The  collagenous  substances  of 
our  tissues  are  not  formed  from  the  collagenous  but  from  the 
proteid  constituents  of  food.  But  the  gelatins  in  food  are,  as 
a  matter  of  fact,  split  up  and  oxidized ;  they  produce  kinetic 
energy. 

Inspired  oxygen  must  also  be  reckoned  among  the  food-stuffs. 
It  is  the  only  one  which  enters  our  tissues  as  a  free  element. 
It  never  becomes  an  integral  constituent  of  our  tissues,  unless 
the  loosely  combined  oxygen  in  the  oxyhemoglobin  of  the 
blood-corpuscles  may  be  considered  so,  but  it  is  the  most  pro- 
ductive source  of  energy. 

We  have  therefore  to  distinguish  three  classes  of  food- 
stuffs : — 

1.  Those  which  serve  as  sources  of  energy,  and  which  can 
replace  the  exhausted  constituents  of  the  body.  To  this  class 
belong  proteids  and  fats. 

2.  Those  which  serve  only  as  sources  of  energy.  To  this 
class  belong  carbohydrates,  gelatins,  oxygen. 

3.  Those  which  serve  only  to  repair  the  waste  of  tissue,  and 

^  [This  opinion  must  be  received  with  some  reserve,  since  it  has  been  shown 
that  the  proximate  constituents  of  all  cells  are  the  very  complex  bodies,  tissue- 
fiVjrinogens,  nucleo-albumins,  &c.,  classed  together  under  the  term  conjugated 
proteids.  In  nearly  all  cases,  these  substances  yield  a  carbohydrate  as  one  of  the 
products  of  their  decomposition,  and  we  must  therefore  assume  that  carbohydrate 
forms  a  necessary  integral  constituent  of  the  molecule.  Even  egg-albumin,  one 
of  the  commonest  of  the  so-called  proteids,  contains  a  carbohydrate  moiety.  In 
light  of  these  results,  it  becomes  doubtful  whether  any  tissue,  even  muscle,  can 
utilize  carbohydrates  directly  for  the  production  of  energy,  or  whether  these 
substances  must  not  first  be  built  up  to  form  part  of  the  living  material  of  the 
cell.] 


THE    FOOD    OF    MAN  43 

not  as  sources  of  energy.     To  this  class  belong  water  and  the 
inorganic  salts. 

Our  knowledge  is  at  present  too  limited  to  permit  of  our 
giving  a  satisfactory  and  sharply  defined  classification  of  food- 
stuffs. 

When  a  substance  is  split  up  and  oxidized  in  our  body,  we 
do  not  know  whether  the  kinetic  energy  thereby  set  free  is 
really  used  up  in  the  performance  of  normal  functions,  or 
whether  it  is  given  out  as  superfluous  heat.  In  the  latter 
case,  the  substance  could  not  be  regarded  as  a  nutrient  material, 
as  it  would  be  of  no  possible  service  to  our  organism.  Alcohol 
may  perhaps  be  cited  as  an  example.  In  order  to  be  of  use 
in  the  performance  of  a  normal  function,  a  substance  must 
split  up  and  be  consumed  at  the  right  time,  at  the  right 
place,  in  a  definite  tissue.  But  we  are  not  yet  in  a  position  to 
follow  out  the  course  of  the  substances  taken  up  so  closely  as 
this. 

It  must  moreover  be  borne  in  mind  that  certain  substances, 
belonging  to  the  second  division,  may  indirectly  assist  in  the 
building  up  of  cells,  by  protecting  the  substances  of  the  first 
class  from  decomposition  and  oxidation.  Fats  sometimes  come 
under  the  first,  and  sometimes  under  the  second  heading ;  for, 
besides  serving  as  stores  of  energy  in  the  tissues,  they  are  of 
great  use  in  another  way.  The  carbohydrates  have,  as  we 
shall  see,  the  power  of  changing  into  fats  in  the  animal  body, 
thus  coming  into  the  first  instead  of  the  second  class.  In 
short,  the  division  is  merely  provisional. 

We  will  now  consider  the  separate  group  of  food-stuffs  in 
somewhat  greater  detail,  beginning  with  proteids. 

Proteids  may  be  regarded  as  the  most  important  food- 
stuffs, in  so  far  as  they  are  the  only  organic  food-stuffs  of  which 
it  can  with  certainty  be  affirmed  that  they  are  indispensable, 
and  that  they  cannot  be  replaced  by  any  other  nutrient  material. 
They  are  to  be  found  in  every  animal  and  vegetable  tissue  ;  they 
form  the  chief  part  of  every  cell ;  they  are  never  absent  from 
any  vegetable  or  animal  food. 

The  various  kinds  of  proteid  which  occur  in  the  different 
animal  and  vegetable  tissues  present  great  differences  in  their 
chemical  and  physical  properties.  The  question  is  therefore  : 
What  is  included  under  the  name  proteid  ?  Does  it  correspond 
to  a  clearly  defined  group  of  bodies?  What  have  all  varieties 
of  proteid  in  common,  and  what  distinguishes  them  from  all 
other  organic  substances? 

First,  all  proteids  resemble  one  another  in  being  composed 
of  the  same  five  elements,  in  proportions  of  weight  not  very 


44  LECTURE    IV 

remote  from  each  other,  and  which  vary  within  the  following 
limits,  according  to  the  analyses  hitherto  made  of  the  different 
proteids : — 

Carbon ,  50.0  to  55.0  per  cent. 

Hydrogen 6.6  "     7.3       " 

Nitrogen 15.0  "  19.0       " 

Sulphur 0.3  "    2.4       " 

Oxygen 19.0  "  24.0       " 

Secondly,  all  proteids  are  alike  in  never  occurring  in  true 
solution.  Numerous  clear  liquids,  containing  proteids,  are 
found  in  plants  and  animals,  or  may  be  artificially  produced. 
But  the  fact  that  the  proteid  does  not  diffuse  through  animal 
membranes  proves  that  it  is  not  really  dissolved  in  these  liquids. 
The  substances  that  are  thus  only  apparently  soluble  have  been 
termed  "  colloids  "  by  Graham.^ 

If  a  solution  of  sodium  silicate  be  poured  into  a  vessel  con- 
taining a  large  excess  of  dilute  hydrochloric  acid,  the  silicic 
acid  thus  set  free  remains  apparently  dissolved.  By  dialysis, 
the  sodium  chlorid  thus  formed  and  the  excess  hydrochloric 
acid  may  be  got  rid  of,  when  a  clear  solution  of  pure  silicic 
acid  will  remain  in  the  dialyzer.  The  silicic  acid  may  amount 
to  14  per  cent,  of  the  solution  without  its  becoming  thick  and 
turbid  ;  it  is  readily  poured  out.  But  a  few  bubbles  of  carbonic 
acid  passed  through  this  solution  suffice  to  coagulate  the  silicic 
acid,  which  is  precipitated  in  the  form  of  a  jelly.^  Grimaux^ 
prepared  a  2.26  per  cent,  solution  of  silicic  acid,  which  was 
more  stable,  and  which  did  not  clot  either  in  cold  or  upon 
warming  when  carbonic  acid  was  passed  through,  but  did  so 
when  heated,  after  the  addition  of  common  salt  or  of  Glauber's 
salt. 

The  hydrate  of  alumina  is  soluble  in  a  watery  solution  of 
aluminium  sesquichlorid.  If  such  a  solution  be  placed  in  the 
dialyzer,  the  chlorid  diffuses  out,  and  the  solution  of  pure 
alumina  remains  in  the  dialyzer  as  a  clear,  readily  transferable 
fluid.  This  solution  coagulates  as  soon  as  a  small  quantity  of 
any  salt  is  added.  A  2  or  3  per  cent,  solution  of  alumina  can 
be  made  to  clot  by  the  addition  of  a  few  drops  of  spring  water ; 
it  coagulates  when  poured  from  one  glass  into  another,  unless 
the  glass  has  immediately  before  been  washed  out  with  distilled 
water.* 

In  a  similar  way  as  with  the  alumina,  oxid  of  iron  may  be 

^Th.  Graham,  Phil.  Trans.,  vol.  cli.  part  i.  p.  183  :   1861. 

2  Graham,  loc.  cit.,  p.  204. 

3  Grimaux,  Gompt.  rend.,  vol.  xcviii.  p.  1437  :  1884. 
■*  Graham,  loc.  cit.,  p.  207. 


THE    FOOD    OF    MAN  45 

obtained  as  a  ölear  blood-red  apparent  solution  which  is  also 
very  prone  to  coagulate/ 

Grimaux  found  that  an  ammoniacal  solution  of  oxid  of 
copper  also  behaves  like  a  colloidal  substance,  that  it  does  not 
diffuse,  and  that  it  coagulates  on  dilution  with  water,  on  the 
addition  of  magnesium  sulphate  or  of  dilute  acetic  acid,  or 
when  exposed  to  a  temperature  of  from  40°  to  50°  C.^ 

Many  organic,  as  well  as  these  inorganic  colloidal  substances, 
and  all  proteids,  have  the  property  of  appearing  in  two  forms, 
in  apparent  solution  or  in  a  coagulated  form.  The  conditions, 
under  which  the  proteids  pass  from  one  modification  to  the  other, 
are  very  varying,  and  offer  a  method  of  classifying  and  dis- 
tinguishing the  many  different  kinds  of  proteid.^  Some  of 
them  may,  under  appropriate  conditions,  be  kept  in  solution 
by  water  alone ;  to  these  proteids  belong  serum-albumin  and 
egg-albumin.  Other  kinds  of  proteid  require  the  addition  of 
alkaline  chlorids  in  order  to  dissolve  them ;  such  are  the 
globulins  which  are  found  in  the  blood,  in  muscle,  in  the  white 
and  yolk  of  egg,  and  probably  in  the  protoplasm  of  every  cell. 
If  blood-serum  be  put  in  a  dialyzer,  the  salts  which  hold 
the  serum-globulins  in  solution  diffuse  out,  and  the  globulins 
separate  on  the  dialyzer  as  finely  flocculent  coagula,  but  the 
serum-albumin  remains  dissolved  in  the  pure  water.*  There 
are  other  varieties  of  proteid  which  cannot  be  held  in  solution 
by  alkaline  chlorids,  but  only  by  basic  alkaline  salts,  in  which 
case  neutralization  of  the  alkalies  with  acids  causes  precipita- 
tion. The  casein  of  milk  and  the  artificial  alkali-albumins 
belong  to  this  category.  Lastly,  we  come  to  the  proteids 
which  are  so  prone  to  coagulate,  that  they  do  so  as  soon  as  life 
is  extinct  in  the  tissues  to  which  they  belong.  The  coagulation 
of  the  blood  and  the  phenomenon  of  muscular  rigidity  after 
death  are  connected  with  this  fact.  It  even  appears  that  these 
kinds  of  spontaneously  coagulable  albumin  exist  in  every 
animal  and  vegetable  cell.  All  proteids,  without  exception, 
pass   from   the    soluble   into  the   coagulated   modification  by 

*  Graham,  loc.  cit.,  p.  208. 

2 Grimaux,  loc.  cit.,  p.  1435. 

3  A  complete  enumeration  of  all  kinds  of  proteid  and  their  distinguishing 
reactions  would,  I  fear,  weary  the  beginner,  so  I  will  refer  him  to  the  article 
"  Eiweisskörper  "  (Proteids),  in  Ladenburg's  "  Handwörterbuch  der  Chemie."  In 
this  article  E.  Drechsel  has  given  a  very  complete  description  and  classification 
of  the  varieties  of  proteid,  with  a  careful  account  of  the  literature  of  the  subject 
(249  treatises). 

■*  Aronstein,  "  Ueber  die  Darstellung  salzfreier  Albuminlösungen,"  Dissert.  : 
Dorpat,  1873;  and  Pfliiger's  Arch.,  vol.  viii.  p.  75:  1873.  See  also  A.  E.  Biirck- 
hardt,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xvi.  p.  322 :  1883 ;  and  G.  Kauder 
ibid.,  vol.  XX.  p.  411 :  1886. 


46  LECTUßE    IV 

exposure  to  the  boiling-point,  provided  they  have  a  neutral  or 
weakly  acid  reaction,  and  if  neutral  alkaline  salts  be  present  in 
considerable  quantities.  Silicic  acid  and  many  other  colloids, 
as  already  stated,  act  in  the  same  manner. 

Concerning  the  inorganic  colloidal  substances,  we  know 
that  besides  occurring  in  these  two  modifications  they  also 
appear  in  nature  in  a  third,  viz.,  the  crystalline  form :  silicic 
acid  as  rock-crystal,  alumina  as  ruby,  oxid  of  iron  as  specular 
iron  ore. 

This  fact  justifies  us  in  hoping  to  obtain  proteids  likewise 
in  a  crystalline  state.  Not  until  we  succeed  in  so  doing,  shall 
we  be  certain  of  having  chemical  individuals  to  deal  with,  and 
in  a  position  to  ascertain  and  compare  their  composition.  The 
analysis  and  examination  of  pure  proteid  crystals  and  of  all 
their  products  of  decomposition  would  form  the  keynote  of 
physiological  chemistry. 

Histologists  have  long  been  on  the  track  of  crystalline 
proteid.  Under  the  microscope  may  be  seen  embedded  in  the 
seeds  and  glands  of  certain  plants,  little  granules  which  have 
the  appearance  of  incompletely  formed  crystals,  and  are  there- 
fore termed  crystalloids,  or  aleuron-crystals.  Similar  structures ' 
may  be  seen  in  the  yolk  of  egg  of  many  animals,  the  so-called 
yolk-plates.  By  mechanical  means,  such  as  shaking  the  finely 
chopped  materials  with  ether  and  other  liquids,  by  washing, 
filtering,  etc.,  these  crystalloids  may  be  isolated  and  obtained  in 
considerable  quantities.  They  give  the  proteid  reactions  and 
behave  like  globulins ;  they  are  soluble  in  a  solution  of 
common  salt.^  Maschke^  has  succeeded  in  recrystallizing  the 
crystalloids  of  the  para  nut  (Bertholletia  excelsd).  They  dis- 
solved in  water  at  from  40°  to  50°  C,  and  the  albumin  separated 
out  into  crystals  upon  concentration  of  the  solution.  Schmiede- 
berg ^  obtained  crystalline  compounds  of  the  same  proteid  with 
alkaline  earths,  the  crystalloids  being  mostly  soluble  in  distilled 
water  at  from  30°  to  35°  C.  When  a  stream  of  carbonic  acid 
is  passed  through  the  clear  filtered  solution,  globulin  is  precip- 
itated. If  this  precipitate  is  treated  with  magnesia  and  water, 
the  magnesia  compound  of  the  globulin  is  dissolved.  From 
this  solution,  when  concentrated  at  from  30°  to  35°  C,  the 
magnesia  compound  of  the  globulin  is  separated  out  as  well- 
formed  peculiarly  glistening  polyhedral  crystals,  of  the  size  of 
poppy-seeds.     If  a  little  calcium  chlorid  or  barium  chlorid  be 

^Th.  Weyl,  Zeitschr.  f.  physiol.  Chem.,  vol.  i.  p.  84:  1877;  containing  also 
an  account  of  the  earlier  literature  of  the  subject. 
2  O.  Maschke,  Botan.  Zeitg.,  p.  411 :  1859. 
^O.  Schmiedeberg,  Zeitschr.  f.  physiol.  Chem.,  vol.  i.  p.  205:  1877. 


THE    FOOD    OF    MAN  47 

added  to  the  solution  before  concentration,  we  obtain  the 
calcium  and  barium  salts  of  the  globulin  in  fine  crystals. 

The  fact  that  these  crystals  are  not  free  proteid,  but  com- 
pounds of  proteid  with  substances  of  known  atomic  weight, 
presents  a  great  advantage,  in  that  it  enables  us  to  make  an 
exact  analysis  of  this  compound,  and  thus  determine  the  molec- 
ular weight  of  the  proteid. 

DrechseP  found  1.40  per  cent.  MgO  in  the  crystals  of  the 
magnesia  compound,  which  he  obtained  according  to  Schmiede- 
berg's  method,  drying  them  at  110°  C.  From  this,  the  molec- 
ular weight  of  the  proteid  has  been  reckoned — 

.       100-1.40    ^^23^^_ 


40  1.4 

By  the  following  alteration  in  Schmiedeberg's  method, 
Drechsel  succeeded  in  more  perfectly  crystallizing  the  magnesia 
compound.  Instead  of  concentrating  the  solution,  he  intro- 
duced it  into  a  dialyzer,  which  he  placed  in  absolute  alcohol. 
In  proportion  as  the  alcohol  took  the  place  of  the  water, 
crystalline  granules  continued  separating  out  of  the  solution. 
The  determination  of  the  magnesia  in  the  crystals  dried  at 
110°  C.  gave  1.4f3  per  cent.  MgO,  or  nearly  the  same  as  in  the 
first  preparation.  The  molecular  weight  of  the  proteid  thus 
calculated  is  2757.  On  the  other  hand,  the  amount  of  water 
varied  in  each  preparation,  the  first  yielding  7.7  per  cent.,  the 
second  13.8  per  cent,  of  water,  both  at  110°  C. 

By  a  similar  method,  with  the  alcohol  dialyzer,  Drechsel 
succeeded  in  producing  a  sodium  compound  of  the  same  glob- 
ulin. At  110°  C.  this  yielded  15.5  per  cent,  of  water,  and 
contained  in  a  dry  state  3.98  per  cent.  Na20.  From  this  the 
proteid  molecule  is  found  to  be  equal  to  1496,  or  nearly  half  as 
great  as  in  the  calculation  from  the  magnesia  compound.  If 
the  smaller  molecular  weight  be  accepted,  we  must  conceive 
that  a  bi-valent  atom  of  magnesium  links  two  molecules  of 
proteid.  If  we  accept  the  double  weight,  the  molecule  must 
contain  two  hydrogen  atoms,  which  are  replaced  by  sodium 
atoms.  The  amount  of  incinerated  proteid  was  moreover 
much  too  small  to  allow  of  an  exact  estimate  of  the  molecular 
weight.  The  absolute  amount  of  the  MgO  weighed  0.0050  and 
0.0065  grm.;  that  of  the  NagCOg  weighed  0.0773  grm.  It  would 
be  of  great  interest  to  determine  with  accuracy  the  relation  of 
sulphur  to  sodium  by  a  series  of  careful  analyses,  in  which  large 
quantities  of  proteid  were  incinerated.  Supposing  that  no 
whole  number  of  sulphur  atoms  went  to  one  atom  of  sodium, 

^E.  Drechsel,  Journ.  f,  prakt.  Cliem.  N.F.,  vol.  xix.  p.  331 :  1879. 


48 


LECTURE   IV 


but  a  whole  number  and  a  fraction,  then  the  denominator  of 
the  fraction  would  have  to  be  multiplied  by  the  equivalent  of 
the  albumin  molecule,  calculated  from  the  proportion  of  sodium. 
No  one  has  hitherto  been  found  to  undertake  such  a  trouble- 
some experiment,  and  we  therefore  know  nothing  concerning 
the  size  of  proteid-molecules. 

The  most  thorough  investigations  upon  proteid-crystals  have 
been  carried  out  by  G.  Grübler,^  under  Drechsel's  guidance. 
They  succeeded  in  recrystallizing  the  crystalloids  of  pumpkin- 
seeds  by  preparing  at  40°  C  saturated  solutions  of  globulin  in 
salt  solutions,  such  as  sodium  chlorid,  ammonium  chlorid, 
magnesium  sulphate,  from  which  the  albumin  separated  out  in 
crystals  on  very  slow  cooling.  These  crystals  were  regular 
octahedra,  and  when  incinerated  left  only  0.11  to  0.18  per 
cent,  of  ash,  which  consisted  of  alkalies,  lime,  magnesia,  iron, 
and  phosphoric  acid.  When  incinerated  with  potash,  0.23  per 
cent.  PjO,  was  obtained. 

The  elementary  analysis  of  Griibler's  proteid-crystals  gave  ' 
the  following  mean,  obtained  from  a  series  of  analyses  which 
agreed  well  with  each  other  : — 


Carbon   .    . 
Hydrogen 
Nitrogen    . 
Sulphur 
Oxygen  .    . 
Ash     ... 


Proteid-crystals  from 

sodium  chlorid 

solution. 


53.21 
7.22 

19.22 
1.07 

19.10 
0.18 


Proteid-crystals  from 

ammonium  chlorid 

solution. 


53.55 
7.31 

19.17 
1.16 

18.70 
0.11 


Proteid-crystals  from 

magnesium  sulphate 

solution. 


53.29 
6.99 

18.99 
1.13 

19.47 
0.13 


Grübler  has  also  produced  a  crystalline  combination  of  the 
same  proteid  with  magnesia :  the  crystals  separating  out  on 
slow  cooling  of  a  solution  (obtained  at  40°  C.)  of  the  proteid 
and  magnesia  in  water.  The  crystals  showed  the  following 
composition : — 

Dry  matter.    Matter  free  from  ash. 

Carbon 52.66  52.98 

Hydrogen 7.20  7.25 

Nitrogen 18.92  18.99 

Sulphur 0.96  0.97 

Oxygen 19.74  19.81 

Ash 0.52 

MgO 0.45 


1  G.  Grübler,  "  Ueber  ein  krystallinisches  Eiweiss  der  Kürbissamen,"  Journ, 
f.prakt.  Chem.,  vol.  xxiii.  p.  97:  1881. 


THE    FOOD    OF    MAN  49 

The  following  formula  for  the  magnesium  compound  of  globulin 
may  be  made  out  from  the  percentage  composition  : — 

^1170^1920^3600332^8^^  Sa- 
lt is  to  be  regretted  in  this  analysis  that  the  quantity  of  in- 
cinerated proteid  was  again  far  too  small  for  an  exact  estimate 
of  the  magnesium  and  sulphur.  The  absolute  weight  of  the 
barium  sulphate  was  0.0521  grm.,  that  of  the  pyrophosphate  of 
magnesia  0.0166  grm. 

If  we  assume  the  presence  of  only  one  atom  of  magnesium 
in  the  magnesium  compound,  as  Grübler  did  in  his  computa- 
tion, then  the  size  of  the  molecule  would  be  8848.  But  our 
calculation  shows  that  for  each  atom  of  magnesium  we  must 
claim  2f  atoms  of  sulphur. 

40   "~0.45'    ^"~3* 

The  molecule  of  the  magnesium  compound  must  therefore  be 
taken  as  three  times  larger.  It  is  conceivable  that  the  three 
bivalent  magnesium  atoms  may  link  four  proteid  molecules, 
and  that  only  two  atoms  of  sulphur  are  contained  in  each. 
Every  proteid  molecule  would  then  have  the  following  com- 
position : — 

^292^481-'-^  9o'-'83^2" 

From  this  point  of  view,  we  attain  to  the  smallest  molecular 
weight  of  which  analysis  admits.  But  this  supposition  is  quite 
arbitrary,  and  the  molecular  weight  probably  a  multiple  of  that 
calculated. 

Ritthausen,^  adopting  the  methods  of  Drechsel  and  Grübler, 
produced  crystalline  proteid  from  hemp  and  castor-oil  seeds. 
The  elementary  analysis  gave  the  following  percentage  com- 
position : — 

Globulin  from  Globulin  from 

hemp  seed.  castor-oil  seed. 

Carbon 50.92 50.85 

Hydrogen 6.91 6.97 

Nitrogen 18.71 18.55 

Sulphur 0.82 0.77 

Ash 0.11 0.057 

Oxygen 22.53 22.80 

Hemoglobin,^  the  red  coloring  matter  of  the  blood,  also 
belongs  to  the  proteid   compounds  capable  of  crystallization. 

1  Ritthausen,  Journ.f.prakt.  Chem.,  N.  F.,  vol.  xxv.  p.  130 :  1882. 

*  The  discoverer  of  the  hemoglobin  crystals  was  A.  Boettcher,  and  the  first 
analyses  of  them  were  carried  out  by  my  revered  teacher,  Carl  Schmidt,  in 
Dorpat.    See  A.  Boettcher,  "  Ueb.  Blutkrystalle  "  :  Dorpat,  1862. 
4 


50  LECTURE    IV 

This  substance  forms  the  chief  constituent  of  the  red  blood- 
corpuscles,  and  is  the  compound  of  a  proteid  with  a  body  of 
known  composition  containing  iron,  called  hematin.  An  exact 
analysis  of  completely  pure  hemoglobin  crystals  has  been 
carried  out  by  Zinoflfsky,^  who  went  on  recrystallizing  the 
hemoglobin  crystals  obtained  from  horse's  blood,  until  the  dry 
residue  of  the  solution  showed  the  same  amount  of  iron  as  the 
dry  crystals.  The  elementary  analysis  of  these  crystals  yielded 
the  following  results  : — 

Carbon 51.15 

Hydrogen     .  .    .    .    .  • 6.76 

Nitrogen • 17.96 

Sulphur 0.389 

Iron 0.336 

Oxygen 24.425 

The  relation  of  the  sulphur  atom  to  the  iron  atom  may, 
from  Zinoffsky's  analysis,  be  calculated  thus — 

x.32_  0.3890  _ono 

""56^-073358'     ^-^•"^• 

Exactly  two  atoms  of  sulphur  combine  with  one  atom  of  iron, 
and  the  formula  of  the  hemoglobin  is  found  to  be — 

If  the  molecule  of  the  hematin,  C^gHajN^O^Fe,  be  subtracted, 
the  formula  of  the  proteid  is  obtained — 

A.  Jaquet^  found  that  exactly  three  atoms  of  sulphur  go  to 
one  atom  of  iron  in  the  hemoglobin  of  dog's  blood.  The 
analysis  gave  the  formula  : — 

After  subtraction  of  the  hematin  it  is  : — 

*-'726H]i71^  194S30214' 

The  calculation  is  not  quite  exact,  because  the  splitting  up 
of  the  hemoglobin   into  proteid  and  hematin  occurs  only  by 

^O.  Zinoffsky  (Bunge's  laboratory),  "  Ueber  die  Grösse  des  Hämoglobin- 
moleküls," Dissert. :  Dorpat,  1885;  reprinted  in  the  Zeitschr.  f.  physiol.  Chem., 
vol.  X.  p.  16:  1885. 

2  Alfred  Jaquet  (Bunge's  laboratory),  "  Beitr.  z.  Kenntniss  des  Blutfarb- 
stoflfes,"  Dissert.:  Basel,  1889;  or  the  Zeitschr.  f.  physiol.  Chem.,  vol.  xii.  p. 
285:  1888. 


THE    FOOD    OF    MAN  51 

the  absorption  of  water  and  oxygen.^  A  few  hydrogen  and 
oxygen  atoms  must  therefore  be  added  to  the  above  proteid  for- 
mulae. Nevertheless  they  are  perhaps  the  most  exact  that  have 
been  computed  from  the  proteid  analyses  hitherto  made,  and 
may  serve  for  present  guidance. 

Harnack  ^  has  produced  and  analyzed  a  proteid  compound 
which,  though  amorphous,  is  probably  pure.  Harnack  precipi- 
tated neutral  solutions  of  egg-albumin  with  solutions  of  cop- 
per, and  obtained  the  noteworthy  result  that,  although  the 
quantitative  relation  of  the  albumin  and  of  the  copper  salt 
varied  greatly,  yet  in  the  precipitates  the  albumin  combined 
with  the  oxid  of  copper  was  only  found  in  two  perfectly 
definite  proportions.  The  precipitates  contained  either  from 
1.34  to  1.37,  a  mean  of  1.35  per  cent.  Cu,  or  from  2.56  to 
2.68,  a  mean  of  2.64  per  cent.  Cu  ;  in  one  case  therefore  ex- 
actly twice  as  many  copper  atoms  as  in  the  other. 

The  complete  elementary  analysis  gave  a  mean  from  a 
series  of  estimates  agreeing  well  with  each  other  : — 

I.  II. 

Carbon 52.50  51.43 

Hydrogen 7.00  6.84 

Nitrogen 15.32  15.34 

Sulphur       1.23  1.25 

Copper 1.35  2.64 

According  to  the  first  analysis,  the  relation  of  the  sulphur  atom 
to  the  copper  atom  may  be  calculated  as — 

X.32      1.23  ^  _ 

6374=  1:36  ■     "  =  ^-^^^- 

The  second  analysis  makes  x=  0.938.  In  these  analyses  also, 
the  incinerated  residue  was  much  too  small  to  allow  a  determi- 
nation of  the  copper  and  sulphur.^  A  more  exact  determina- 
tion of  these  elements  is  urgently  required.  From  his  analyses, 
Harnack  reckons  the  formula  for  the  first  compound : 

Loew*  has  produced  two  silver  compounds  of  egg-albumin, 
which  correspond  to  Harnack's  copper  compounds ;  one  con- 

1  Concerning  this,  see  Max  Lebensbaum,  Wien.  Sitzungsher.,  vol.  xcv.  part 
ii.,  March,  1887.  In  this  vrork,  carried  out  in  Berne  under  Nencki's  direction, 
there  is  also  an  account  of  the  earlier  literature  on  the  splitting  up  of  hemo- 
globin. Compare  also  Hoppe-Seyler,  Zeitschr.f.  physiol.  Chem.,  vol.  xiii.  p.  477: 
1889. 

^  E.  Harnack,  Zeitschr.  f.  physiol.  Chem.,  vol.  v.  p.  198 :  1881. 

^  Compare  O.  Loew,  Pfliiger's  Arch.,  vol.  xxxi.  p.  393 :  1883. 

^  O.  Loew,  loc.  cit.,  p.  402. 


52  LECTURE    IV 

tained  from  2.2  to  2.4  per  cent.  Ag,  the  other  a  mean  of  4.3 
per  cent.  Ag.  Taking  Harnack's  figures  for  the  amount  of 
copper,  the  silver  equivalent  may  be  computed  =  2.3  per  cent, 
and  4.5  per  cent.  These  facts  go  to  prove  that  Harnack's  and 
Loew's  preparations  were  true  chemical  entities.  It  is  to  be 
regretted  that  Loew  has  not  made  any  elementary  analysis  of 
his  preparations. 

Finally  Franz  Hofmeister^  has  succeeded  in  crystallizing 
egg-albumin  itself.  The  white  of  the  hen's  egg  contains  two 
kinds  of  proteid  substances,  one  belonging  to  the  albumin  and 
the  other  to  the  globulin  group.  If  the  globulins  are  precipi- 
tated by  a  concentrated  solution  of  ammonium  sulphate,  and 
the  filtrate  from  this  precipitate  be  allowed  to  stand  for  some 
days  exposed  to  slow  evaporation,  small  spheroids  separate  out, 
which  are  composed  of  incompletely  formed  crystals.  By  dis- 
solving and  recrystallizing  these  spheroids,  albumin  is  obtained 
in  well-formed,  needle-shaped  crystals.  Analysis  of  these  crys- 
tals gave  the  following  composition  : — 

C 53.3 

H 7.3 

N 15.0 

S 1.1 

O 23.3 

Using  Hofmeister's  method,  Bondzynski  and  Zoja  ^  prepared 
albumin  crystals  from  white  of  egg,  and  succeeded,  by  frac- 
tional crystallization,  in  demonstrating  the  existence  in  white  of 
egg  of  several  distinct  albumins,  differing  by  their  solubilities 
in  ammonium  sulphate  solutions  as  well  as  by  their  coagula- 
tion temperatures  and  their  rotatory  power  on  polarized  light. 
On  the  other  hand,  the  elementary  composition  was  identical  in 
all  the  fractions.  In  one  preparation  the  lime  and  phosphoric 
acid  were  also  determined,  and  the  following  composition  was 
arrived  at : — 

C 52.3 

H 71 

N 15.5 

S 1.6 

O 23.5 

PA 0.29 

CaO 0.26 

The  ash  forms  part  of  the  constitution  of  the  proteid  molecule. 
Proteid  free  from  ash  never  occurs  in  nature.       Although  it 

■■  Franz  Hofmeister,  Zeitschr.  f.  physiol.  Chem.,  vol.  xiv.  p.  165  :  1889,  and 
vol.  xvi.  p.  187 :  1892.     Compare  also  S.  Gabriel,  idem,  vol.  xv.  p.  456  :  1891. 

2  St.  Bondynski  and  L.  Zoja,  Zeitschr.  f. physiol.  Chem.,  vol.  xix.  p.  1 :  1894. 


THE    FOOD    OF    MAN  53 

can  be  prepared  artificially/  we  have  not  yet  succeeded  in  crys- 
tallizing it. 

Bondzynski  and  Zoja  could  not  obtain  the  globulins  of 
white  of  egg  in  a  crystalline  form  ;  the  only  precipitates  they 
obtained  were  in  the  form  of  the  spheroids,  which  are  the  first 
stage  in  the  crystallization  of  albumin. 

In  blood-serum,  as  in  the  white  of  egg,  we  also  find  albu- 
mins and  globulins  (compare  Lect.  XIV.).  In  albuminuria  both 
escape  into  the  urine,  but  in  very  varying  proportions.  Until 
quite  recently  no  spontaneous  crystallization  of  the  proteids  in 
the  urine  had  ever  been  observed.  It  seems  however  that  the 
presence  of  one  kind  of  proteid  hinders  the  crystallization  of  the 
other,  since  in  a  recent  case  of  marked  albuminuria,  published 
by  Byrom  Bramwell  and  Noel  Paton,^  where  almost  only  glob- 
ulin was  present,  this  globulin  could  be  easily  crystallized  by 
Hofmeister's  method.  Indeed  at  times  it  was  sufficient  to 
allow  the  urine  to  stand  for  one  or  two  days  to  obtain  a  crystal- 
line silky  precipitate,  which  under  the  microscope  was  seen 
to  consist  of  beautiful  rhombic  prisms.  The  analysis  of  these 
globulin  crystals  gave  the  following  results  : — 

C 51.9 

H 6.9 

N 16.1 

S 1.2 

O 33.9 

Finally,  we  may  mention  that  Gürber  ^  and  Michel  *  have 
succeeded  in  preparing  beautiful  crystals  of  the  albumin  of 
blood-serum.  [The  technique  of  the  crystallization  of  proteids 
has  been  much  simplified  by  the  discovery  of  Hopkins  that  the 
addition  of  a  trace  of  acid  much  favors  the  ease  of  crystalliza- 
tion. Full  details  of  the  method  will  be  found  in  the  original 
paper.^  By  this  method  it  is  possible  to  prepare  crystals,  in 
any  quantity  and  within  a  few  hours,  both  of  egg-  and  serum- 
albumin.  By  washing  these  crystals  with  an  acid  solution  of 
sodium  chlorid,  the  whole  of  the  ammonium  sulphate  may  be 
removed,  showing  that  the  presence  of  this  salt  is  not  necessary 
to  the  integrity  of  the  crystalline  form.] 

'  See  letter  written  by  Liebig  to  Wöhler,  Not.  16,  1848  (Aus  J.  Liebig's  u. 
Fr.  Wöhler's  Briefwechsel,  vol.  i.  p.  323  ;  Braunschweig,  Vieweg  u.  Sohn,  1888)  ; 
E.  Hamack,  Ber.  d.  deut.  chem.  Ges.,  vol.  xxiii.  p.  40 :  1890,  and  vol.  xxv.  p.  204  : 
1892;  K.  Bülow,  Pflüger's  Arch.,  vol.  Iviii.  p.  207:  1894. 

2  Byrom  Bramwell  and  D.  Noel  Baton,  Reports  fr.  the  Lab.  of  Roy.  Coll.  of 
Physicians,  Edin.,  vol.  iv.  p.  47  :  1892. 

^  A.  Gürber,  Sitzungsber.  d.  phys.-med.  Ges.  zu  Würsburg,  p.  143 :  1894. 

*  A.  Michel,  Verh.  d.  phys.-med.  Ges.  zu  Würzburg,  vol.  xxix.  No.  3  :  1895. 

^  F.  Gowland  Hopkins  and  S.  N.  Pinkus,  "Crystallization  of  Proteids," 
Joum.  of  Physiol.,  vol.  xxiii.  p.  130  :  1898. 


54  LECTURE    IV 

The  formulae  of  the  proteids  already  quoted  are  : — 

Egg-albumin,  C^^^ü^^^l^^p^ß^. 
Proteid  in  hemoglobin  of  horse,  CggpHj^ggMg^oOg^^Sg. 
Proteid  in  hemoglobin  of  dog,  C!y26-'^ii7i-^i94^2u^3* 
Globulin  from  pumpkin-seeds,  CgggH^g^lSTg^OggSg. 

Thus  if  we  select  the  most  careful  and  exact  of  all  the  analyses 
hitherto  made  of  the  purest  preparations  of  different  proteids, 
we  find  that  they  give  very  varying  quantitative  compositions, 
and  that  they  particularly  differ  in  the  amount  of  sulphur. 

So  far  as  they  have  been  investigated,  proteids  show  a 
certain  agreement  in  their  products  of  decomposition.  It  ap- 
pears that  the  different  proteids  are  composed  of  the  same 
proximate  constituents  combined  in  varying  proportions. 
On  heating  the  proteids  with  baryta  water,  they  break  up 
under  hydration  into  numerous  compounds,  which  are 
almost  all  of  known  constitution.  The  principal  are  car- 
bonic acid,  oxalic  acid,  acetic  acid,  ammonia,  sulphuretted 
hydrogen,  sulphuric  acid,  and  a  number  of  amido-acids,  such  as 
aspartic  acid,  leucin,  tyrosin,  as  well  as  lysin,  lysatin,  &c.  The 
same  amido-acids,  as  well  as  ammonia  and  the  bases  lysin, 
lysatin,  azginin,  and  histidin,^  also  present  themselves  on  boil- 
ing the  proteids  with  acids  and  under  the  influence  of  fer- 
ments. We  shall  have  to  discuss  the  products  produced  by 
the  splitting  up  of  proteids  more  fully  when  we  come  to  treat 
of  the  chemistry  of  the  urine  ;  we  shall  then  also  consider  the 
decomposition  of  the  nitrogen  compounds  in  the  organism  (vide 
Lecture  XIX.). 

Another  group  of  food-stuffs,  the  gelatiniferous  or  col- 
lagenous SUBSTANCES,  are  closely  related  to  the  proteids  in 
chemical  qualities  ;  but  their  physiological  import  is  quite  dif- 
ferent. 

Gelatiniferous  substances  are  the  chief  constituents  of  con- 
nective tissue,  of  bone  and  cartilage,  and  therefore  form  an 
important  part  of  the  food  of  carnivorous  and  omnivorous  ani- 
mals. 

Gelatins,  like  proteids,  are  colloids  containing  nitrogen  and 
sulphur,  and  may  likewise  occur  in  two  modifications — one 
apparently  dissolved  but  not  diffusible ;  the  other  coagulated. 
But  the  conditions  of  the  transit  from  one  modification  to 
another  are   exactly  the  reverse.     All    proteids  coagulate,  as 

1  Kossel,  Sitzungsber.  d.  Ges.  z.  Bef'drd.  d.  ges.  Naturwiasensch.,  Marburg,  p. 
56 :  July,  1897.  Here  also  references  will  be  found  to  the  earlier  authors  wh<v 
have  dealt  with  these  bases. 


THE    POOD   OF   MAN  55 

already  described,  at  boiling-point,  with  neutral  or  weakly  acid 
reaction,  and  in  the  presence  of  salts ;  the  gelatins,  on  the  con- 
trary, become  soluble  under  these  circumstances,^  and  on  cool- 
ing the  solution  of  gelatin  thus  formed  again  coagulates.  Solu- 
tions of  proteid  are  precipitated  by  mineral  acids,  but  not  so 
solutions  of  gelatin.  The  gelatin  of  cartilage  is  certainly  pre- 
cipitated by  very  dilute  mineral  acids,  but  dissolved  by  an  ex- 
cess, thus  behaving  in  the  opposite  manner  to  the  globulins, 
which  are  soluble  in  very  dilute  (1  per  1000)  hydrochloric  acid, 
but  are  again  precipitated  by  an  excess  of  it. 

If  therefore  varieties  of  proteid  or  gelatin  are  soluble  or 
coagulable  under  opposite  conditions,  we  need  not  be  surprised 
to  find  that,  under  similar  conditions  in  the  organism,  the  one 
occurs  invariably  in  the  soluble,  the  other  only  in  the  solid, 
modification.  Proteids  are  found  in  our  bodies  only  in  a  liquid 
state.  In  this  form  they  are  the  main  constituents  of  the 
blood-plasma  and  of  lymph,  or  they  occur  in  that  peculiar 
semi-liquid  modification  common  to  all  those  tissues  which 
play  an  active  part  in  the  functions  of  our  bodies :  the  con- 
tractile contents  of  muscle-fibers,  the  axis-cylinders  of  nerve- 
fibers,  the  protoplasm  of  all  cells  which  we  must  not  conceive 
as  rigid  structures,  but  as  engaged  in  a  constant  state  of  active 
ameboid  movement.^  The  collagenous  substances,  on  the 
contrary,  are  found  in  our  tissues  only  in  the  rigid  modifica- 
tion ;  they  form  the  supports  and  the  framework  of  our  bodies, 
viz.,  bone,  cartilage,  ligaments,  and  connective  tissue  of  all 
kinds. 

But  here  I  must  guard  against  a  misunderstanding,  lest  it 
should  appear  that  I  am  identifying  the  gelatiniferous  constit- 
uents of  the  tissues  with  coagulated  gelatin.  In  the  conversion 
of  collagenous  tissues  into  solutions  of  gelatin,  a  fundamental 
change  takes  place,  possibly  a  decomposition  accompanied  by 
hydration,  and  the  gelatin  is  not  reconverted  into  the  collage- 
nous substances  on  coagulation. 

The  percentage  composition  of  the  varieties  of  gelatin  is 
nearly  the  same  as  that  of  the  proteids.  At  the  same  time,  it 
is  characteristic  of  the  former  that  they  are  somewhat  poorer  in 

^  It  is  not  until  after  the  phosphates  and  carbonates  of  lime  and  magnesia 
have  been  extracted  with  dilute  hydrochloric  acid  at  a  low  temperature,  that  the 
gelatin  of  bone  is  dissolved  in  boiling  water,  and  especially  under  increased  pres- 
sure. The  salts  of  lime  and  magnesia  appear  to  be  chemically  united  with  the 
collagenous  substance. 

2  As  already  mentioned,  proteid  is  found  in  the  solid  form,  deposited  in  crys- 
tals, only  in  the  yolk  of  egg  and  in  the  seeds  and  bulbs  of  plants.  These  crystal- 
loids are  however  not  integral  constituents  of  the  living  tissue,  but  dead  material, 
the  store  of  nutriment  for  the  future  development  of  the  germ. 


56 


LECTURE    IV 


carbon  and  richer  in  oxygen ;  they  are  products  of  the  initia- 
tion of  the  breaking  up  and  oxidation  of  the  proteids  in  the 
animal  body.  According  to  the  analyses '  hitherto  made,  the 
percentage  composition  of  the  gelatins  varies  within  the  follow- 
ing limits  : — 


Carbon  , 
Hydrogen. 
Nitrogen  . 
Sulphur.  . 
Oxygen    . 


Gelatin  from  bone 
or  connective  tissue. 


49.3—50.8 

6.5—  6.6 

17.5—18.4 

—  0.56(?) 
24.9—26.0 


Chondrin. 


47.7—50.2 
6.6—  6.8 

13.9—14.1 
0.4—  0.6(?) 

29.0—31.0 


Albumin. 


50.0—55.0 
6.6—  7.3 

15.0—19.0 
0.3—  2.4 

19.0—24.0 


We  know  for  a  fact  that  certain  compounds  of  the  aromatic 
class,  rich  in  carbon  and  which  issue  in  the  form  of  tyrosin 
and  indol  from  the  decomposition  of  proteids,  are  absent  in  the 
gelatiniferous  substances.^  It  is  moreover  a  fact  that  the  heat- 
equivalent  of  gelatin  is  lower  than  that  of  the  proteids  f  that 
therefore  a  part  of  the  potential  energy  introduced  into  the 
animal  body  by  proteid  is  already  consumed  during  its  conver- 
sion into  gelatin-yielding  substances.  We  should  therefore,  ä 
priori,  expect  to  find  that  the  gelatins  do  not  replace  the  pro- 
teids of  the  food,  and  that  they  cannot  form  the  proteids  of 


^  Fr.  Hofmeister,  Zeitschr.  f.  physiol.  Chem.,  vol.  ii.  p.  299:  1878. 

2  The  absence  of  tyrosin  explains  the  fact  that  gelatin  does  not  give  Millon's 
reaction,  which  is  common  to  all  proteids  (red  coloration  on  boiling  with  nitrate 
of  mercury,  with  the  addition  of  fuming  nitric  acid).  All  aromatic  oxy-acids 
and  their  derivatives,  to  which  tyrosin  belongs,  give  this  reaction.  On  the  other 
hand,  compounds  which  are  wanting  in  proteids  occur  among  the  decomposition- 
products  of  gelatins.  Amido-acetic  acid  (glycin,  glycocoll),  which  has  hitherto 
not  been  shown  to  exist  among  the  decomposition-products  of  any  proteid,  is  ob- 
tained from  the  gelatin  of  bones  and  connective  tissue,  on  boiling  with  alkalies  and 
acids,  and  in  putrefaction.  From  cartilage  Schmiedeberg  {Arch.  f.  exp.  Path.  u. 
Pharm.,  vol.  xxviii.p.  355  :  1891)  isolated  small  quantities  of  a  compound,  which 
on  boiling  with  dilute  acids  was  dissociated  with  the  formation  of  sulphuric  acid, 
acetic  acid,  glycuronic  acid,  and  glycosamin.  These  results  explain  the  older 
statements  as  to  the  occurrence  of  sugar  or  '  reducing  substances '  among  the  de- 
composition-products of  chondrin.  On  the  products  of  the  decomposition  of  pro- 
teids and  gelatin,  see  further,  M.  Nencki,  "  Ueber  die  Zersetzung  der  Gelatine 
und  des  Eiweisses  bei  der  Fäulniss  mit  Pankreas,"  Bern.,  1876 ;  and  Sitzungsher. 
d.  Akad.  d.  Wissensch.  in  Wien,  Math.-natur.  Klasse,  vol.  xcviii.  Pt.  2,  May  9, 
1889 ;  Jules  Jeanneret,  Journ.  f.  prakt.  Chem.,  N.  F.,  vol.  xv.  p.  353 :  1877  ;  Leon 
Selitrenny,  Sitzungsber.  d.  Akad.  d.  Wissensch.  in  Wien,  Math.-natur.  Klasse,  vol. 
xcviii.  Pt.  2,  b.  Dec.  12,  1889  (from  Neucki's  laboratory) ;  Ed.  Buchner  und  Th. 
Curtius,  Ber.  de  deutsch,  chem.  Ges.,  vol.  xix.  p.  850  :  1886  ;  and  R.  Maly,  Sit- 
zungsher, d.  Kais.  Akad.  d.  Wissensch.  in  Wien,  Math.-natur.  Klasse,  vol.  xcviii. 
Jan.  6,  1889. 

*  Danilewsky,  Centralblatt  f.  d.  med.  Wissensch.,  Nos.  26  and  27:  1881. 


THE    FOOD    OF    MAN  57 

the  tissues.  Such  a  conversion  would  be  opposed  to  the  whole 
tendency  of  animal  metabolism,  which  is  essentially  a  process 
of  decomposition  and  of  oxidation.  The  conversion  of  gelatin 
into  albumin  would  be  one  of  synthesis  and  reduction.  The 
results  of  Voit's  experiments/  showing  that  gelatin  cannot 
replace  proteid  in  the  food,  are  in  agreement  with  the  ä  •priori 
deduction.  When  Voit  fed  dogs  exclusively  on  gelatin,  or  on 
gelatin  and  fat,  they  excreted  more  nitrogen  than  they  took  in 
with  their  food ;  they  therefore  used  up  the  proteids  of  their 
tissues.  But  if  to  a  small  amount  of  the  proteid  in  the  food, 
which  was  not  by  itself  sufficient  to  prevent  a  loss  of  tissue-pro- 
teid,  gelatin  was  added,  the  nitrogenous  equilibrium  was  re- 
stored. The  gelatin  therefore  had  preserved  the  proteid  of  the 
tissues  from  decomposition  ;  it  acts  as  a  '  proteid  sparer.'  This 
proteid-sparing  action  is  also  shared  by  fats  and  carbohydrates  ; 
but,  as  Voit's  experiments  have  shown,  not  in  the  same  degree 
as  by  gelatin. 

It  has  recently  been  supposed  that  the  gelatin  might 
perhaps  replace  the  proteid  if  tyrosin  were  at  the  same  time  ad- 
ministered. We  now  know  that  the  contrast  in  the  metabo- 
lism of  animals  and  plants  is  not  so  complete  as  was  formerly 
supposed.  Hence  there  was  the  d  priori  possibility  that  pro- 
teid might  be  formed  by  synthesis  from  gelatin  and  tyrosin. 
The  first  experiments  ^  appeared  even  to  favor  this  supposition; 
but  on  careful  repetition,  a  negative  result  was  obtained. 
Lehmann  ^  fed  two  rats  on  a  mixed  diet  of  gelatin,  rice-starch, 
butter,  meat-extract,  and  bone-ash ;  and  six  rats  on  the  same 
diet  with  the  addition  of  tyrosin.  They  all  died  at  about  the 
same  time,  from  forty-seven  to  seventy  days  afterwards.  Thus 
these  experiments  also  tend  to  show  that   no  proteid  can   be 


1  Voit,  Zeitschr.  /.  Biolog.,  vol.  viii.  p.  297 :  1872.  The  historical  introduction 
to  this  treatise,  showing  the  numerous  errors  into  which  any  one  would  neces- 
sarily fall  from  the  experiments,  formerly  made  to  decide  the  question  concerning 
the  nutritive  value  of  gelatin,  is  highly  instructive  and  interesting.  Compare 
also  the  more  recent  paper  on  this  subject :  Zeitschr.  f.  Biolog.,  vol.  x.  p.  203 : 
1874.  We  cannot  attain  to  a  complete  understanding  of  the  significance  of 
food-stuffs  until  we  get  to  know  all  the  processes  of  metabolism.  We  ought 
therefore  properly  to  leave  the  consideration  of  the  import  of  the  various  food- 
stuffs to  the  last  chapter  of  physiological  chemistry.  But  this  diiSculty  can  in 
no  way  be  surmounted,  for  every  chapter  of  physiology  presupposes  other  chap- 
ters. It  appears  to  me  advisable  to  arouse  the  reader's  interest  at  the  start  by 
pointing  out  the  importance  in  vital  processes  of  those  substances  whose  gradual 
changes  and  ultimate  destination  in  the  animal  body  must  be  the  foundation  of 
all  future  study. 

^L.  Hermann  und  Th.  Escher,  Vierteljahr  sehr,  der  naturforsch.  Ges.  in 
Zürich,  p.  36 :  1876. 

^  Karl  B.  Lehmann,  Sitzungsber.  d.  Ges.  f.  Morphol.  u.  Physiol,  in  Jlünchen  : 
1885. 


58  LECTURE    IV 

produced  from  gelatin,  although  we  know,  on  the  other  hand, 
that  all  gelatin-yielding  tissues  of  the  body  are  formed  from 
proteid.  This  is  seen  in  the  growth  of  the  herbivora,  and  of 
the  young  animal  in  its  suckling  stage,  since  their  food  contains 
proteids  but  no  gelatin. 

Gelatin,  as  such,  is  to  be  found  only  in  cooked  food.  Of 
the  gelatin-yielding  tissues,  connective  tissue  is  easily  digested, 
and  is  therefore  an  important  element  of  food.  Meat,  which 
consists  to  a  great  extent  of  connective  tissue,  disappears 
almost  entirely  in  the  alimentary  canal  of  man.  The  digesti- 
bility of  cartilage  and  bone  was  long  doubted,  until  it  was 
proved,  by  experiments  in  Voit's  laboratory,^  that  dogs  fed  on 
cartilage  ejected  but  a  very  inconsiderable  amount  in  the  feces. 
A  large  part  (as  much  as  53  per  cent.)  of  the  collagenous 
substance  of  the  bones  did  not  reappear  in  the  feces.  We  do 
not  know  how  far  the  digestive  organs  of  man  are  capable  of 
dealing  with  cartilage  and  bone,  as  no  experiments  have  been 
made  to  ascertain  this. 

Keratin,  the  chief  constituent  of  the  epidermis,  of  hair, 
nails,  claws,  hoofs,  horns,  and  feathers,  was  formerly  classed 
with  the  collagenous  substances.  But  keratin  is  distinguish- 
able from  the  gelatins,  as  well  as  from  the  proteids,  by  its  high 
percentage  of  sulphur  (from  4  to  5  per  cent.)  but  more 
especially  from  the  gelatins  by  the  fact  that  tyrosin  makes  its 
appearance  among  its  products  of  decomposition.  According 
to  this  last  property  keratin  should  be  classed  among  the  pro- 
teids. The  keratins  of  the  various  tissues  are  probably  not 
identical  and  not  chemical  entities,  but  mixtures  of  different 
substances.  Keratin  does  not  come  under  our  consideration 
as  a  food ;  according  to  previous  experiments  it  appears  in- 
capable of  being  digested  by  the  mammal.^  Certain  insects 
can  digest  keratin.  The  caterpillar  of  the  clothes-moth 
apparently  feeds  almost  entirely  upon  keratin.  Wherever 
therefore  keratin  is  rendered  soluble,  it  can  take  the  place  of 
proteid.  The  chief  constituent  of  elastic  tissue, '  elastin,'  which 
was  likewise  formerly  classified  under  the  same  heading  as 
gelatin,  now  stands  by  itself:  on  decomposition,  it  yields  a 
small  amount  of  tyrosin.^     Elastic  tissue  is  almost  completely 


1  J.  Etzinger,  Zeitschr.f.  Biolog.,  vol.  x.  p.  84 :  1874. 

^  Knieriem,  "On  the  Value  of  Cellulose  in  the  Animal  Organism,"  p.  6, 
Jubilee  Essay:  Riga,  1884.  Reprinted  in  the  Zeitschr.  f.  Biolog.,  vol.  xxi.  p. 
67:  1885. 

ä  For  the  composition  and  properties  of  elastin,  vide  R.  H.  Chittenden  und 
A.  S.  Hart,  Zeitschr.  /.  Biolog.,  vol.  xxv.  368:  1889.  The  earlier  literature  is 
here  quoted. 


THE    FOOD    OF    MAN  59 

digested  by  dogs.^  As  regards  human  beings,  we  must  mention 
an  experiment  made  by  Horbaczewski  ^  on  a  patient  with 
gastric  fistula.  Powdered  elastin  in  a  small  bag  was  introduced 
through  the  fistula,  and  was  found  to  be  partly  dissolved  in 
twenty-four  hours. 

1  Etzinger,  loc.  cit.    Compare  also  L.  Morochowetz,  St.  FetersMirger  med. 
Wochenschr. :   No.  xv.,  1886;    A.  Ewald  und  "W.  Kühne,   Verhandlungen  des 

natur.-histor.  med.  Vereins  zu  Seidelberg,  N.  F.,  vol.  i.  p.  441 :  1877  ;  and  Chit- 
tenden und  Hart,  loc.  cit. 

2  J.  Horbaczewski,  Zeitschr.  f.  physiol.  Chem.,  vol.  vi.  p.  330:  1882. 


LECTURE  V 

THE     ORGANIC     FOOD-STUFFS      (continued) CARBOHYDRATES 

AND    FATS SIGNIFICANCE    OF    THE    THREE    MAIN 

GROUPS    OF    ORGANIC    FOOD-STUFFS 

We  will  now  turn  our  attention  to  two  main  groups  of  food- 
stuifs  which  oifer  a  contrast  to  the  two  last  mentioned,  in  being 
free  from  nitrogen  and  sulphur — the  fats  and  the  carbohy- 
drates.^ They  agree  with  one  another  in  being  made  up  of  the 
same  three  elements  :  carbon,  hydrogen,  and  oxygen.  But  the 
quantitative  composition  is  well  known  to  be  quite  diiferent ;  the 
fats  are  much  poorer  in  oxygen,  and  richer  in  carbon  and  hydro- 
gen.    Therefore  the  heat-equivalent  of  the  fats  is  much  greater. 

The  heat-equivalent  of  the  organic  substances  can  not  be 
exactly  computed  from  the  known  heat-equivalents  of  carbon 
and  hydrogen,  because,  of  the  amount  of  heat  which  is  set  free 
by  the  union  of  the  oxygen  with  the  carbon  and  hydrogen,  a 
part  which  is  used  up  in  the  separation  of  the  hydrogen  atoms 
from  the  carbon  atoms,  and  of  the  carbon  atoms  from  each 
other.  This  amount  of  heat  may  vary  greatly  in  different  com- 
pounds, because  the  atoms  are  more  or  less  firmly  combined 
with  each  other,  and  varying  amounts  of  heat  are  set  free  by 
their  union.  Metameric  compounds  are  known  to  produce  dif- 
ferent heat-equivalents.  Hence  the  heat-equivalents  of  food 
stuffs  have  been  determined  by  direct  calorimetric  methods, 
first  by  Frankland,^  then  by  an  improved  method  by  Stoh- 
mann  ^  and  his  pupil  Rechenberg,*  lastly  by  Danilewsky  ^  and 
by  Rubner.^    In  the  following  table  I  give  the  values  ascertained 

1  Both  here  and  in  all  subsequent  remarks,  a  knowledge  of  the  chemical 
properties  of  the  carbohydrates  and  fats  is  presupposed,  as  these  compounds  are 
usually  described  at  sufficient  length  in  the  text-books  of  organic  chemistry. 

2  Frankland,  Philos.  Mag.,  vol.  xxxii.  p.  182  :  1866. 

^Stohmann,  Journ.f.  prakt.  Chem.,  N.  F.,  vol.  xix.  pp.  115-142:  1879;  and 
Landwirthschaftl.  Jahrb.,  pp.  531-581 :  1884;  Zeitschr.  f.  Biolog.,  vol.  xxxi.  p. 
364:  1895. 

*von  Eechenberg,  Journ.f.prakt.  Chem.,  N.  F.,  vol.  xxii.  pp.  1-45,  223-250: 
1880. 

5  Danilewsky,  Pfliiger's  Arch.,  vol.  xxxvi.  p.  237  :  1885. 

«  Rubner,  Zeitschr.  f.  Biolog.,  vol.  xxi.  pp.  250,  337 :  1885. 

60 


THE    ORGANIC    FOOD-STUFFS  61 

by  the  above-mentioned  authors.  By  the  side  of  each  figure 
will  be  found  the  first  letters  of  the  author's  name.  The  heat- 
equivalents  of  carbon,  hydrogen,  and  of  a  few  decomposition- 
products  of  food-stuffs,  are  also  added  to  the  table  for  reference  in 
future  remarks.  The  unit  of  heat  (calorie)  is  that  quantity  of  heat 
required  to  raise  the  temperature  of  one  gramme  of  water  1  °  C. 


Heat-Equivalents  of  One  Gramme  of  Substance  Expressed 
IN  Calories. 

Hydrogen F.  andS.» 34,462 

Stearic  acid,  CigHjgOj Ech 9886 

Rub 9745 

«'         F.  and  S 9717 

Beef  fat D 9686 

Olive  oil St 9455 

Pig's  fat Rub 9423 

Stearic  acid     . .  St 9412 

Fat  (human  and  animal),  the  aver- 
age of  a  number  of  approximate 

figures,  9319-9429 St 9372 

Butter St 9179 

Charcoal F.  and  S 8080 

Ethylalcohol F.  and  S 7184 

"             Berthelot 6980 

Leucin     .   .       St.  and  h.^ 6525 

B.  and  A.  3 6537 

Fibrin  (vegetable) D.                 6231 

Elastin    .    .                   St.  and  L 5961 

Hemoglobin  (from  horse) D.             5949 

Vegetable  fibrin St.  and  L 5942 

Serum-albumin St.  and  L 5918 

Tyrosin B.  and  A 5916 

Hemoglobin  (from  horse)   .....  B.  and  A 5915 

Syntonin         St.  and  L 5908 

Hemoglobin St.  and  L 5885 

Casein St.  and  L 5858 

"          D 5855 

Legumin            St.  and  L 5793 

Blood  fibrin D 5772 

Vitellin St.  and  L 5745 

Egg-albumin St.  and  L 5735 

Milk -casein      (three      preparations 

5754-5693),  average                 ...  St 5715 

Egg-albumin          B.  and  A 5690 

Crystallized   albumin   (from  pump- 
kin-seeds)    St.  and  L 5672 

Hippuric  acid St.  and  L 5668 

"           "       B.  and  A 5659 

Butyric  acid F.  and  S 5647 


1  Favre  and  Silbermann,  Ann.  d.  Chim.  et  d.  Phys.,  vol.  xxxiv.  p.  357 :  1852. 

2  F.  Strohmann  and  H.  Langbein,  Joum.  f.  prakt.  Chem.,  N.  F.,  vol.  xliv.  p. 
336:  1891. 

3  Berthelot  and  A.  Andre,  Ann.  d.  Chim.  et  d.  Phys.,  series  vi.  vol.  xxii.  pp. 
5  and  25:  1891. 


62  LECTURE   V 

Heat-Eqtjivaients  of  One  Gramme  of  Substance  Expressed 
IN  CaI/ORIEs  {continued). 

Paraglobulin  (from  horse's  serum) 5634 

Casein                 .                   B.  and  A 5629 

Crystallized   proteid    (prepared   by 

Grübler  from  pumpkin  seeds)    .    .  St 5595 

Egg-albumin      ( two      preparations, 

5556  and  5597),  mean  .    .                .St 5577 

Blood    fibrin    (three    preparations, 

5487-5536),  average            ....  St 5508 

Gelatin  (from  isinglass)       .            .    .  D 5493 

Ossein B.  and  A 5414 

Chrondrin       B.  and  A 5346 

Peptone       St.  and  L 5299 

Caffein         St.  and  L 5231 

Chondrin St.  and  L 5131 

Ossein .    .              St.  and^L 5040 

Peptone  ( prepared  by  Drechsel )    .    .  D 4914 

Chondrin D 4909 

Peptone D 4876 

Sarcosin          St.  and  L 4506 

Starch Ech 4479 

Erythrodextrin Ech 4325 

Glycerin St 4305 

Creatin  (anhydrous) St.  and  L 4275 

Cane  sugar D.          4176 

"       "         Ech 4173 

Maltose  anhydride Ech 4163 

Lactose  anhydride Ech 4162 

Cellulose  (from  Swedish  filter-paper)  St .  4146 

Starch St 4116 

Cane  sugar     .    .            ....              St 3959 

Lactose  hydrate,  C12H22O11,  HjO   .    .  Ech 3945 

Dextrose  anhydride  .    .            ....  Ech 3939 

Maltose  hydrate,  C^^K^fin,  H2O  .    .  Ech 3932 


Guanin 
Lactose  anhydride 
Creatin  -|-  HjO 
Dextrose  anhydride 
Lactose  hvdrate 


St.  and  L 3892 

St 3877 

St.  and  L 3714 

St.             3692 

St 3667 


Dextrose  hydrate,  CgHijOg,  HjO         Ech 3567 

Acetic  acid             .                F.  and  S 3505 

Aspartic  acid St 3423 

Glycocoll        =    ...  St 3050 

Succinic  acid      Ech 2996 

"           "        St.             2937 

Aspartic  acid B.  and  A 2911 

"          " St.  and  L 2899 

Uric  acid St.  and  L 2750 

"      "        Frankl 2645 

"       "        St.             2620 

Urea                St.  and  L.        ...  2542 

"        D 2537 

"        St 2465 

Frankl 2121 

Tartaric  acid St 1744 

"          " Ech 1407 

Oxalic  acid     .    .    .  • Ech 659 

"        "        St 569 


THE    ORGANIC    FOOD-STUFFS  63 

In  the  case' of  non-nitrogenous  food-stuifs,  the  same  amounts 
of  heat  are  produced  in  our  bodies  as  in  the  calorimeter,  be- 
cause the  ultimate  products  are  the  same  ;  but  it  is  different 
in  the  case  of  food-stuffs  containing  nitrogen.  Nitrogen 
is  liberated  in  a  free  state  from  combustion  in  the  calorim- 
eter ;  on  the  other  hand,  it  issues  from  the  decomposition 
and  oxidation  of  the  body  as  an  organic  compound,  in  union 
with  a  part  of  the  carbon  and  hydrogen,  and,  in  the  case  ot 
man,  principally  as  urea.  The  amount  of  urea  which  can  be 
formed  from  the  proteid  is  about  one-third  of  the  weight  of 
the  proteid.  In  order  therefore  to  ascertain  the  heat-equiva- 
lent of  the  proteid  in  our  organism,  we  must  deduct  one-third 
of  the  heat-equivalent  of  urea  from  that  of  the  proteid.  But 
this  figure  would  come  out  rather  too  high,  because  the  nitrogen 
leaves  our  body  not  only  as  urea,  but  partly  as  a  compound 
containing  both  more  carbon  and  more  hydrogen.  We  must 
therefore  subtract  at  least  800  units  of  heat  from  the  heat- 
equivalent  of  the  proteids  in  the  above  table,  and  we  then  ob- 
tain figures  which  are  only  a  little  higher  than  those  of  the  car- 
bohydrates. As  a  store  of  energy  in  our  bodies  therefore,  the 
carbohydrates  are,  in  a  quantitative  respect,  about  equivalent 
to  the  proteids.  The  heat-equivalent  of  fats,  on  the  other  hand, 
is  twice  as  great. 

Little  has  as  yet  been  ascertained  as  to  the  manner  in  which 
the  organs,  in  the  performance  of  their  various  functions,  util- 
ize the  potential  energy  acquired  with  the  food.  As  muscle 
consists  chiefly  of  proteid,  it  was  a  plausible  supposition  that 
this  substance  was  the  source  of  muscular  work.  This  view 
was  maintained  by  Liebig,  who  contrasted  the  food-stuffs  con- 
taining no  nitrogen — the  fats  and  carbohydrates — as  "  respira- 
tory foods"  with  the  proteids  as  "plastic  foods."  He  taught 
that  the  former  served  mainly  to  generate  heat.  At  the  present 
time  we  know  that,  in  muscular  work,  the  excretion  of  nitrogen 
is  increased  only  in  a  slight  degree,  but  that  the  excretion  of 
carbonic  acid  and  the  absorption  of  oxygen  is  notably  increased; 
that  therefore  muscle  works  principally  with  material  free  from 
nitrogen.  We  know  that  a  store  of  carbohydrates  is  to  be 
found  in  the  muscles  in  the  form  of  glycogen,  and  that  this 
store  disappears  during  work.  It  thus  appears  that  the  carbo- 
hydrates serve  as  the  chief  sources  of  energy  in  muscle.^  The 
fats  and  the  carbohydrates  may  replace  each  other,  but  only 
within  certain  limits ;  they  do  not  appear  to  play  exactly  the 
same   part.     This  is  proved  by  their  simultaneous  appearance 

^  The  question  as  to  the  source  of  muscular  energy  will  be  fully  treated  in 
Lecture  XXIII. 


64  LECTURE   V 

in  the  milk  of  all  Carnivora,  omnivora,  and  herbivora.  It  is 
farther  proved  by  the  instinctive  desire  for  the  addition  of  fat 
to  a  diet,  however  abundant  in  carbohydrates  it  may  be,  and 
the  desire,  on  the  other  hand,  for  the  addition  of  carbohydrates 
to  the  richest  fat-diet. 

The  fats  are,  at  any  rate,  the  most  fertile  sources  of  heat. 
Concerning  the  importance  of  animal  heat  in  vital  functions, 
we  know,  so  far,  that  all  chemical  processes,  as  well  as  the 
interchange  of  energy  connected  with  them,  and  the  functions 
of  the  body  dependent  upon  them,  are  more  intense  at  a  higher 
temperature.  The  fact  that  the  functions  of  the  nervous  system, 
and  of  the  muscles  especially,  are  performed  more  rapidly  at  a 
higher  temperature,  may  be  easily  demonstrated,  as  is  well 
known,  on  Poikilothermie  animals. 

It  has  not  yet  been  ascertained  which  functions  of  the  body 
are  aided  by  the  decomposition  and  oxidation  of  the  large 
amount  of  proteid,  which  no  other  food-substance  can  replace. 
It  is  a  matter  of  experience,  that  each  person  must  be  daily 
supplied  with  at  least  100  grms.  of  proteid  in  one  form  or 
another.  If  he  eats  less  than  this  amount,  he  must  use  part 
of  the  proteid  of  his  tissues,  however  large  a  quantity  of  fat 
and  carbohydrates  he  takes  as  well.^  The  fats  and  carbohy- 
drates can  only  act  in  a  certain  degree  as  substitutes  for  the 
proteids. 

We  know  indeed  that  the  elements  of  our  tissues  which  are 
rich  in  proteids  undergo,  like  all  unicellular  organisms,  a  rapid 
change  of  generations ;  that  increase,  death  of  one  part,  growth 
and  division  of  another,  follow  each  other  in  uninterrupted 
succession.  In  the  epidermis  (the  tissue  most  convenient  for 
observation),  we  see  the  older  cells  continually  dying  off  and 
being  replaced  by  the  proliferation  of  under  layers.  The  same 
process  has  been  traced  in  the  epithelial  cells  of  the  intestine 
and  of  certain  glands.  A  glance  at  a  section  of  bone  shows 
that  newly-formed  concentric  lamellae  are  continually  growing 
into  the  older  system  as  it  becomes  absorbed.  We  shall  see, 
when  we  come  to  consider  the  processes  of  absorption  in  the 
intestine  (Lectures  XIII.  and  XV.),  that  the  leucocytes  also 
undergo  rapid  growth  and  destruction.     Why  should  not  the 

1  From  numerous  experiments  recently  communicated,  it  appears  that  when 
a  large  amount  of  carbohydrates  is  taken,  much  less  than  100  grms.  of  proteid  is 
almost,  if  not  quite,  sufficient  to  maintain  nitrogenous  equilibrium.  It  is  open 
to  question  however  whether  it  would  be  so  over  a  long  period  of  laborious  work 
and  normal  sexual  life.  Vide  C.  Voit,  E.  Voit  und  Constantinidi,  Zeitschr.  /. 
Biolog.,  vol.  XXV.  p.  232  :  1888;  Hirschfeld,  Virchow's  Arch.,  vol.  cxiv.  p.  301 : 
1888 ;  and  Pfliiger's  Arch.,  vol.  xlix.  p.  428  :  1889  ;  and  Muneo  Kumagawa,  Vir- 
chow's  Arch.,  vol.  cxvi.  p.  370 :  1889.    Compare  also  end  of  Lect.  VIII. 


THE    OEGANIC    FOOD-STUFFS  65 

same  thing  b'e  taking  place  in  the  tissues  hidden  from  our 
observation  ? 

But  the  material  of  the  dying  cells  may  be  used  up  in  the 
growth  of  the  surviving  ones.  The  necessity  for  a  daily  con- 
sumption of  100  grms.  of  proteid  is  incomprehensible,  so  long 
as  we  do  not  know  of  any  function  of  the  body  in  the  per- 
formance of  which  the  chemical  potential  energies  of  the  de- 
stroyed proteid  are  used  up. 

As  we  know  for  a  fact  that  proteid  is  the  only  one  of  the 
three  main  groups  of  food  that  cannot  be  replaced  by  any  other, 
our  choice  and  combination  of  the  articles  of  diet  [must  be 
regulated  by  the  amount  of  proteid  they  contain.  In  the  fol- 
lowing table  ^  may  be  seen  the  average  composition  of  the  most 
important  articles  of  diet,  arranged  according  to  the  quantity 
of  proteid  found  in  them : — 

TABLE  I. 

One  Hundred  Grms.  of  Food  in  a  Natueax,  State  Contain— 

Proteid.  Fats.  Carbohydrates. 

Apples 0.4 — 13 

Carrots 1.1 0.2 9 

Potatoes 2.0 0.1 20 

Human  milk 2.4 4.0  ..    .  6 

Cabbage  (various)  ...    3.3 -0.7 7 

Cow's  milk 3.4 4.0  ..    .  5 

Eice 8.0 0.9 77 

Maize 10.0 4.6 71 

Wheat 12.0 1.7 70 

Egg-albumin 13.0 0.3 — 

Fat  fish  (eel) 13.0 28.0 — 

Fat  pork 15.0 37.0 — 

Yolk  of  egg  .    .    -    .          16.0  .    .    .             32.0      — 

Fat  beef 17.0 26.0 — 

Lean  fish  (pike)          .    .  18.0 0.5 — 

Lean  beef 21.0 1.5 — 

Peas 23.0 1.8 58 


TABLE  II. 
One  Hundred  Gems,  of  Dried  Substances  Contain- 


Apples   ..... 

Proteid. 
...     2.4  ..    . 

Fats. 

Carbohydrates. 
79 

Potatoes     .... 
Rice 

...     8.0 
...    9.0  ..    . 

.     .     0.6       . 
...     1.0  .     . 

...     87 
89 

Carrots 

.    .    ,  10.0  .    .    . 

.    2.0  .    , 

82 

Maize 

.    .    .  11.0  .    .    . 

.    .    .    5.0 

81 

Wheat 

.    .    .  14.0  .    .    . 

...    2.0  .    . 

...    81 

Human  milk    .    . 

.    .    .  18.0  .    .    . 

.    .    .  30.0  .    . 

.    ...    48 

1  The  numbers  are  taken  from  the  work  of  J.  König,  "  Chemie  der  menschli- 
chen Nahrungs- und  Genussmittel,"  2d  edit.  (Berlin,  1882),  in  which  will  be 
found  an  exhaustive  collection  of  all  former  analyses. 

5 


66 


LECTUEE    V 


TABLE  II.    (continued). 


Cabbage 

Proteid. 
.    .    .  26.0  .   .    . 

Fats 
...    5.0  .    . 

Carbohydrates 
.    ...    56 

.    .    .  27.0  .    .    . 

.    2.0  .    . 

.    ...    62 

Cow's  milk    .    .    . 

.    .    .  27.0  .    .    . 

.    .    .  29.0  .    . 

.    ,    .        38 

Fat  pork    .... 

.    .    .  28.0  .    .    . 

.    .    .  71.0  .    . 

Fat  fish 

.    .    .  30.0  .   .    . 

.    .    .  67.0  .    . 

Yolk  of  egg  .    .    . 
Fat  beef     .    . 

.    .    .  33.0  .    .    . 
.    .    .  39.0  .   .    . 

.    .      65.0  .    . 
.    .    .  59.0  .   . 

.    .    .    — 

Lean  beef  .... 

.    .    .  89.0  .   .    . 

...    6.0      . 

Egg-albumin     .    . 
Lean  fish  .... 

.    .    .  89.0  .    .    . 
.   .    .  90.0  .    .    . 

.       .    2.0  ,   . 
...    2.5  .    . 

.    .    .    .    — 

In  the  following  table  we  give  the  amount  which  it  is 
necessary  to  eat  of  the  various  articles  of  diet  in  their  natural 
undried  condition,  in  order  to  convey  100  grms.  of  proteid  into 
our  bodies : — 

TABLE  III. 

One  Hundred  Gems,  op  Peoteid  aee  Contained  in — 

25,000  grms.  apples. 


9000 
5000 
4200 
3000 
3000 
1250 
1000 
800 


carrots, 
potatoes, 
human  milk, 
cabbage, 
cow's  milk, 
rice, 
maize, 
wheat. 


750  grms 

egg-albumin 

750      " 

fat  fish  (eel). 

650     " 

fat  pork. 

620      " 

yolk  of  egg. 

600      " 

fat  beef. 

550     " 

lean  fish. 

480     " 

lean  beef. 

430     " 

peas. 

In  the  following  table  we  give  the  amount  of  dried  articles  of 
food  which  contain  100  grms.  of  proteid  : — 


TABLE  IV. 

One  Hundeed  Gems,  op  Peoteid  aee  Contained  in — 


4200  grms.  dried  apples. 


1250 
1100 
1000 
900 
700 
550 
440 
370 


potatoes. 

rice. 

carrots. 

maize. 

wheat. 

human  milk. 

cabbage. 

peas. 


370  grms.  dried  cow's  milk. 


360 
330 
300 
250 
112 
112 
110 


fat  pork. 

fat  fish. 

yolk  of  egg. 

fat  beef. 

lean  beef. 

egg-albumin. 

lean  fish  (pike). 


If  we  subtract  100  from  the  numbers  given,  we  learn  from 
this  last  table  how  much  of  the  other  solid  constituents,  espe- 
cially carbohydrates  and  fats,  we  must  consume  in  order  to  ob- 
tain 100  grms.  of  proteid.  In  the  following  two  tables  these 
quantities  are  divided  into  carbohydrates  and  fats  ;  in  Table  V. 
they  are  arranged  according  to  increase  of  carbohydrates,  and 
in  Table  VI.  according  to  increase  of  fats. 


THE   ORGANIC   FOOD-STUFFS  67 

TABLE  V. 
With  One  Hundred  Grms.  of  Proteid  we  Take  up  in — 

Carbohydrates.  Fats. 

Cow's  milk 140 107 

Cabbage 220 21 

Peas  230 7 

Human  milk 270 170 

Wheat 580 14 

Maize 740 46 

Carrots 820 20 

Eice      990 11 

Potatoes 1000 8 

Apples 3300 0 

TABLE  VI. 
With  One  Hundred  Grms.  of  Proteid  we  Take  up  in — 

Fats.  Carbohydrates. 

Apples — 3300 

Egg-albumin 2 — - 

Pike 3 — 

Lean  beef 7 — 

Peas 7 230 

Potatoes 8 1090 

Eice 11 990 

Corn 14 580 

Carrots .    .    .    , 20  . 820 

Cabbage 21 220 

Maize 46 740 

Cow's  milk 107 140 

Fat  beef 150 — 

Human  milk 170 270 

Yolk  of  egg 200 — 

Eel  220 — 

Fat  Pork 250 — 

In  forming  an  opinion  from  these  tables  concerning  the 
value  of  the  different  animal  and  vegetable  foods,  the  follow- 
ing must  also  be  taken  into  consideration.  The  amount  of 
proteid  in  most  articles  of  food  has  not  been  accurately  deter- 
mined. The  amount  of  nitrogen  only  has  been  ascertained,  and 
from  this  the  amount  of  proteid  has  been  calculated  under  the 
supposition  that  no  other  nitrogen- compounds  exist  in  food,  and 
that  all  kinds  of  proteids  contain  16  per  cent,  of  nitrogen. 
Both  assumptions  are  wanting  in  precision.  The  amount  of 
nitrogen  in  the  various  proteids  varies,  as  we  have  seen,  from 
15  to  19  per  cent.  The  other  assumption,  that  foods  contain 
no  other  nitrogen-compound,  holds  good  in  the  case  of  the 
grains  of  cereals  and  leguminosse.  But  in  most  of  the  other 
vegetable  food-stuflFs,  ammonia,  nitric  acid,  amides,  amido-acids, 
&c.,  are  found  in  considerable  quantities.     In  certain  kinds  of 


68  LECTURE   V 

vegetables  the  nitrogen  of  these  compounds  amounts  to  more ' 
than  one-third  of  the  total  nitrogen.  ^!^ 

It  would  also  be  a  serious  mistake  to  calculate  the  amount 
of  proteid  from  the  amount  of  nitrogen  in  meat.  This  contains 
a  considerable  quantity  of  gelatin-yielding  substances  which,  as 
I  have  already  pointed  out,  have  a  totally  different  action  in 
nutrition  to  that  of  proteid.  The  collagenous  substances  of 
animal  food  may  be  regarded  as  more  analogous  to  the  carbohy- 
drates of  vegetable  food  than  to  the  proteids.  If  therefore  the 
nutrient  value  of  meat  and  vegetables  be  judged  from  the  above 
tables  according  to  their  relative  amount  of  proteid,  the  value 
of  the  meat  Avill  be  rated  too  highly,  and  that  of  the  vegetables 
not  highly  enough. 

On  the  other  hand  it  must  be  remembered  that  animal  food 
is  much  more  completely  absorbed  than  vegetable  food.  The 
capability  of  absorption  of  the  proteid  in  different  foods  has  of 
late  been  accurately  tested  by  a  careful  comparison  of  the  amount 
of  nitrogen  in  the  nutriment  taken  with  that  in  the  feces.  It 
has  thus  been  ascertained  that  the  proteid  of  the  meat  almost 
entirely  disappears.  A  considerable  part  of  the  proteid  in 
milk  reappears  in  the  feces,  and  a  still  larger  proportion  is  un- 
absorbed  from  vegetables.  The  table  on  p.  69  gives  the  results 
of  these  experiments  on  the  absorption  of  proteid  ;  they  have  all 
been  carried  out  on  human  beings. 

If  the  following  table  be  compared  with  Tables  III.  and 
IV.,  it  appears  scarcely  possible  that  a  man  could  take  up,  in 
the  form  of  vegetables,  the  daily  amount  of  at  least  100  grms. 
of  proteid  necessary  to  maintain  nitrogenous  equilibrium.  The 
potato  appears  especially  unsuited  for  this  purpose ;  5  kgrms. 
must  be  eaten  in  order  to  introduce  100  grms.  of  proteid  into 
the  stomach,  but  7  kgrms.  must  be  consumed  to  allow  of  the 
absorption  of  100  grms.  of  proteid.  English  statisticians  do  in 
fact  show  that  Irish  workmen,  who  live  chiefly  on  potatoes,  eat 
on  an  average  4  to  6.5  kgrms.  each  daily.  This  appears 
scarcely  credible.  The  person  experimented  on  by  Rubner,^ 
a  powerful  soldier,  who  was  accustomed  to  take  large  quantities 
of  potato  when  at  home  in  the  Bavarian  Alps,  could  not 
manage  more  than  from  3  to  3.5  kgrms.,  although  this  monot- 
onous form  of  food  was  prepared  in  various  ways,  with  salt  or 
with  butter,  with  vinegar  and  oil  as  a  salad,  in  the  form  of 
chips,  or  baked ;  and  although  the  man  was  eating  all  day 
long.  The  potatoes  he  ate  contained  only  71.5  grms.  of  pro- 
teid, of  which  23.1  grms.  remained  unabsorbed.  He  could  not 
therefore  maintain  his  nitrogenous  equilibrium,  as  he  gave  out 

^  Rubner,  loc.  cit.,  vol.  xv.  p.  146. 


THE    ORGANIC    FOOD-STUFFS 


69 


Food. 


Beef  (the  same  person  being  experi-\ 

mented  on) j 

Eggs  

Milk  and  cheese  (the  same  person)  . 


Milk  3  ( four  experiments  on  four  dif-  \ 
ferent  people)    J 

"Leguminose"   (flour  from  legumi-") 
nosse  and  cereals)  ....  J 

Macaroni        

Maize 

Peas  and  bread 

Vermicelli 

Savoy  cabbage 

Wheat  bread  .  

Rice 

Kye  bread 

White  bread  (the  same  person)  .    , 

Peas,  shelled   and  well   boiled   (the\ 

same  person) .  J 

Broad  beans,  well  cooked 

Whole  wheat-meal  bread 

Black  break  (rye  bread) 

Potatoes 

Harsford-Liebig  bread 

Carrots  (boiled) 

Lentils 

Bran  bread        

Kye-bran  bread 

Lentils,  potatoes,  and  bread   .... 


Percentage  of  un- 
absorbed  proteid.' 


2.51 
2.8/ 


1.9  [ 
5.7) 


2.9 

2.9 

4. 

3. 

6.5 
7.0 

7.7 
12.0 

iio'.ö} 

11.2 

15.5 
12.0-20.0 

17.1 

18.5 

19.9 

20.4 

22.2 

18.7- 

20.7 

24.6 

25.7. 
f  17.51 
\27.8/ 

30.25 

30.5 

32.0 

32.2 

32.4 

39.0 

40.0 

42.3 

45.4 
53.5 


Author. 


Kubner  ^ 
Kubner 

Eubner 


Eubner 


Strümpell  * 

Rubner 

Eubner 

Woroschiloflf^ 

flubner 

Eubner 

Meyer  ^ 

Eubner 

Meyer 

Eubner 


Eubner 

Prausnitz ' 

Eubner 

Eubner 

Eubner 

Meyer 

Eubner 

Strümpell 

Meyer 
/  Huldgren   and 
1     Landergren  ^ 

Hofmann  ^ 


1  These  figures  are  rather  too  high,  because  the  nitrogen  in  the  feces  is  con- 
tained, not  only  in  the  unabsorbed  food,  but  also  in  the  products  of  metabolism, 
which  are  eliminated  in  the  intestine.  According  to  Rieder's  experiments  with 
non-nitrogenous  food,  the  nitrogen  eliminated  in  the  intestine  amounts  to  8  per 
cent,  of  the  total  nitrogen  excreted  under  these  circumstances.  Zeitschr.  f. 
Biolog.,  vol.  XX.  p.  478 :  1884. 

2  Max  Eubner,  Zeitschr.  f.  Biolog.,  vol.  xiv.  p.  115 :   1879 ;  vol.  xvi.  p.  119 
1880;  vol.  xix.  p.  45:  1883. 

'  Concerning  the  absorbability  of  milk,  see  W.  Prausnitz,  Zeitschr.  f.  Biolog., 
vol.  XXV.  p.  533 :  1889. 

4  A.  Strümpell,  Deutsch.  Arch.  f.  Min.  Med.,  vol.  xvii.  p.  108:  1876. 

^  WoroschilofiF,  Botkin's  Arch.,  vol.  iv.  p.  1 :  1872  (Russian).  Unfortunately 
a  very  inaccurate  account  of  this  useful  work  is  to  be  found  in  the  Berl.  klin. 
Wochenschr.,  p.  90  :  1873. 

*  G.  Meyer,  Zeitschr.  f.  Biolog.,  vol.  vii.  p.  1 :  1871. 

'W.  Prausnitz,  Zeitschr.  f.  Biolog.,  vol.  xxvi.  p.  227:  1890. 

*  E.  Huldgren  and  E.  Landergren,  JYord.  Med.  Arkiv,  p.  21 :  1890. 

^  Fr.  Hofmann,  "  Die  Bedeutung  der  Fleischnahrung  und  Fleiachconserven," 
pp.  11,  44 :  Leipzig,  1880. 


70  LECTUEE   V 

more  nitrogen  through  the  kidneys  than  he  absorbed  from  the 
intestines,  thus  using  up  the  store  of  proteid  in  his  tissues,  i.  e., 
he  was  gradually  dying  of  hunger.  A  sceptical  observer  must, 
however,  concede  the  possibility  that  many  Irish  laborers  may 
consume  5  kgrms.  of  potatoes  and  maintain  their  nitrogenous 
equilibrium.   The  difference  in  individuals  is  of  course  very  great. 

I  wish  further  to  point  out  that  such  a  diet  can  be  better 
borne  by  adults  than  by  children.  Children  have  to  build  up 
an  organism  rich  in  proteid ;  adults  have  only  to  maintain  the 
previous  store,  performing  their  muscular  work  with  the  carbo- 
hydrates, of  which  a  superfluity  is  introduced  with  a  potato- 
diet.  The  frightful  mortality  among  children  of  the  lower 
classes  is  perhaps  largely  due  to  the  want  of  proteid  in  their  food. 

Among  the  more  important  articles  of  vegetable  food,  the 
leguminosse  contain  the  largest  amount  of  proteid.  A  diet  of 
these,  if  properly  prepared,  maintains  nitrogenous  equilibrium. 
This  is  shown  by  the  experiments  Woroschiloff^  made  upon 
himself.  He  lived  for  thirty  days  entirely  upon  peas,  bread, 
and  sugar,  while  at  the  same  time  he  performed  8528  kilogram- 
meters  of  work  per  hour,  for  the  space  of  one  to  three  hours  a 
day,  and  yet  he  showed  no  loss  of  proteid.  The  person  whom 
Rubner  ^  experimented  upon,  also  kept  his  nitrogenous  equilib- 
rium on  a  diet  of  peas. 

If  an  exclusively  vegetable  diet  proves  insufficient,  it  is 
perhaps  caused  less  by  the  want  of  proteid  than  by  the  want 
of  fat.  If  we  glance  at  Table  V.  (p.  67),  we  see  that  the 
relation  of  carbohydrates  to  proteid  is  the  same  in  a  diet  of 
leguminosse  and  cereals  as  in  milk,  with  the  diflPerence  that 
the  former  contain  much  less  fat  than  milk  does.  We  should 
hence  ä  priori  expect  to  find  that  a  man  could  exist  very  well 
upon  cereals  and  leguminosse,  with  the  addition  of  fat,  or  per- 
haps even  upon  cereals  and  fat  only.  Milk  is  the  normal  food 
of  the  infant,  not  of  the  adult.  The  adult  requires,  as  I  have 
just  explained,  relatively  less  proteid  and  more  carbohydrates. 
We  might,  therefore,  conclude  that  the  normal  food  of  the 
adult  would  be  furnished  by  the  proteid  and  carbohydrates,  in 
the  proportion  met  with  in  the  cereals,  and  that  this  diet 
would  only  require  the  addition  of  fat.  This  theory  appears 
to  be  confirmed  by  experience.  The  laborers  in  some  districts 
of  Bavaria,  who  do  the  hardest  work,  are  said  to  live  upon  a 
diet  prepared  from  flour  and  lard.^     This  mode  of  living  would 

'  WoroschilofF,  loc.  cit.  "^TiAihneY,  loc.  cit.,  vol.  xvi.  p.  125 :  1880. 

^H.  Ranke,  "Die  bayr.  Landwirthschaft  in  den  letzten  10  Jahren."  Fest- 
gabe, &c.,  p.  160:  München,  1872;  Liebig,  Sitzungsber.  d.  bayr.  Akad.,  vol.  ii. 
p.  463:  1869;  "  Reden  und  Abhand.,"p.  121.  Compare  also  Ohlmüller,  ZeiiscAr. 
/.  Biolog.,  vol.  XX.  p.  393 :  1884. 


THE   ORGANIC   FOOD-STUFFS  71 

be  the  ideal  of  vegetarians  ^  if  the  fat  were  likewise  obtained 
from  the  vegetable  kingdom,  in  the  form  of  oil,  olives,  nuts, 
cocoa.  From  investigations  made  by  Panum  and  Buntzen,  it 
appears  that  even  a  carnivorous  animal  can  be  nourished  on 
cereals  and  fat ;  a  dog  which  was  fed  exclusively  on  groats  and 
butter  could  be  kept  in  good  health  for  two  months  without 
loss  of  weight.^  Unfortunately  this  experiment  lasted  much  too 
short  a  time. 

The  fat  of  all  food  is  very  completely  absorbed,^  far  more 
so  than  the  proteids.  The  same  is  true  of  all  carbohydrates,^ 
with  the  single  exception  of  cellulose.  This  was  held  to  be 
totally  indigestible  until  quite  recently,  when  it  was  proved 
by  experiments  on  ruminants^  at  the  farm-stations  kept  for 
investigations,  that  from  60  to  70  per  cent,  of  the  woody  fibers 
disappear  from  the  digestive  canal.  At  the  experimental  farm 
of  Tharand,*'  it  was  even  found  that  from  30  to  40  per  cent,  of 
the  cellulose  of  sawdust  and  paper  was  absorbed  by  sheep  when 
mixed  and  eaten  with  hay.  Weiske^  was  the  first  to  make 
experiments  on  human  beings,  which  he  carried  out  on  himself 
and  on  another  person.  He  found  that  one  of  them  digested 
62.7  per  cent.,  the  other  47.3  per  cent.,  of  the  woody  fibers 
in  the  food,  which  consisted  of  carrots,  cabbage,  and  celery. 
Later  on  Knieriem  ^  made  experiments  on  himself,  and  found 
that  he  digested  25.3  per  cent,  of  the  tender  woody  fibers  oi 
lettuce,  but  only  4.4  per  cent,  of  the  tougher  fibers  of  Scor- 
zonera.  The  latter  figure  is  within  the  limits  of  unavoidable 
error.  How  cellulose  undergoes  solution  in  the  intestines,  we 
shall  explain  further  on,  when  we  come  to  the  consideration  of 
the  digestive  processes. 

Cellulose  can  scarcely  be  classed  among  the  food-substances 
of  human  beings.  On  the  other  hand  it  is  of  great  importance 
in  acting  as  a  mechanical  stimulus  to  promote  the  peristalsis  of 
the  intestine.  For  this  reason  cellulose  is  absolutely  essential 
to  animals  with  a  long  intestinal  tract.     If  rabbits  are  fed  on  a 

1 T  have  published  a  detailed  criticism  of  vegetarianism  in  a  small  pamphlet, 
" Der  Vegetarianismus "  (Berlin,  Hirsch wald :  1885). 

^Jahresbericht  über  die  Fortschritte  der  TMerchemie,  vol.  iv.,  of  the  year 
1874,  p.  365 :  Wiesbaden,  1875. 

^Rubner,  loc.  cit.,  vol.  xv.  p.  189. 

*Rubner,  loc.  cit.,  p.  192. 

^Haubner,  Zeitschr.  für  Landwirthschaft,  p.  177:  1855;  Henneberg  and 
Stohmann,  "Beiträge  zur  Begründung  einer  rationellen  Fütterung  der  Wieder- 
käuer," Heft  i. :  1860;  Heftii. :  1863. 

^  "  Der  chemische  Ackersmann,"  pp.  51,  118 :  1860. 

'  H.  Weiske,  Zeitschr.  f.  Biolog.,  vol.  vi.  p.  456  :  1870. 

*  V.  Knieriem,  "  Ueber  die  Verwerthung  der  Cellulose  im  thierischen  Organ- 
ismus," Festschrift :  Riga,  1884.  Also  printed  in  the  Zeitschrift  f.  Biolog.,  vol. 
xxi.  p.  67  :  1885. 


72  LECTURE  V 

diet  containing  no  cellulose,  the  onward  movement  of  the  in- 
testinal contents  ceases,  inflammation  in  the  intestines  ensues, 
and  the  animals  rapidly  die.  But  if  horn-parings  be  added  to 
the  same  food,  nutrition  is  normal.^  These  horn-parings  are,  as 
Knieriem  proved  by  experiments  devoted  to  that  purpose,  abso- 
lutely undigested,  and  can  therefore  only  have  taken  the  place 
of  woody  fiber  in  so  far  as  its  mechanical  properties  were  con- 
cerned. Of  three  mice,  fed  entirely  on  milk,  one  died  after 
forty-seven  days  of  intussusception,  as  dissection  showed.^ 

The  following  are  the  details  of  a  post-mortem  examination 
of  a  rabbit  which  had  died  for  lack  of  cellulose  :  "  The  stomach 
only  contained  mucus,  and  showed  signs  of  incipient  inflamma- 
tion in  the  region  of  the  pylorus ;  the  small  intestine,  full  of 
mucus,  was  much  inflamed  throughout  its  whole  length,  as  was 
also  the  cecum.  The  latter  was  largely  filled  with  excrement  of 
the  consistency  of  putty,  which  adhered  firmly  to  the  wall?  and 
folds  of  the  cecum.  The  diiference  between  these  contents  and 
those  of  the  cecum  of  a  normally  fed  rabbit  is  very  noticeable, 
for  here  the  mass  in  the  cecum  is  pretty  loose,  falling  almost 
completely  away  if  the  intestine  be  bent  backwards,  and  this 
loose  consistency  is  caused  only  by  the  tough  fibers,  by  means  of 
which  the  communication  between  the  anus  and  the  stomach  is 
kept  open.  This  could  hardly  have  been  the  case  in  the  animal 
which  died."  ^ 

The  short  intestine  of  Carnivora  does  not  require  a  mechan- 
ical stimulus  to  produce  peristaltic  action.  The  intestine  of 
human  beings  is  well  known  to  be  of  medium  length ;  a  man's 
life  therefore  is  not  endangered  by  deprivation  of  cellulose, 
although  the  normal  movement  of  the  intestine  might  be  thereby 
impeded.  The  muscular  wall  of  the  intestine  becomes  atrophied 
like  every  other  muscle,  if  it  has  no  work  to  do.  We  must 
therefore  see  that  the  diet  of  human  beings  does  not  lack  woody 
fibers.  The  excessive  fear  of  indigestible  food  which  prevails 
among  the  wealthier  classes  may  lead  to  universal  debility  of 
the  intestinal  muscular  walls.  Habitual  constipation  would 
perhaps  not  be  such  a  common  trouble  if  we  were  accustomed 
from  our  childhood  to  a  dietary  containing  a  sufficient  supply 
of  woody  fiber.  Of  late  years  whole-meal  bread,  which  is  rich 
in  cellulose,  has  been  a  successful  remedy  for  chronic  constipa- 
tion. It  is  well  known  that  an  exclusive  milk  diet  may  occa- 
sion constipation. 

^Knieriem,  loc.  cit.,  pp.  6,  17-19. 

^N.  Lunin  (Bunge's  laboratory),  "  Ueber  die  Bedeutung  der  anorganischen 
Salze  für  die  Ernährung  des  Thieres,"  p.  15,  Dissert. :  Dorpat,  1880.  Also  printed 
in  the  Zeitschr.  f.  physiol.  Chem.,  vol.  v.  p.  37  :  1881. 

3  Knieriem,  loc.  cit.,  p.  17. 


THE    OEGANIC    FOOD-STUFFS  73 

On  the  other  hand  it  is  urged  that  the  rapid  and  continual 
movement  of  the  intestinal  contents  in  consequence  of  the  irri- 
tating action  of  the  woody  fibers  has  one  drawback — the  in- 
complete utilization  of  the  food.  In  fact,  Meyer  ^  has  already 
shown,  by  direct  experiment,  that  it  is  more  economical  to  feed 
on  the  dearer  bread  of  fine  flour  than  on  the  cheaper  bran 
bread.  Fr.  Hofmann  showed  that  the  addition  of  cellulose 
diminishes  the  nutritive  value  of  meat.^  At  the  same  time,  it 
appears  to  me  that  the  advantages  of  food  containing  cellulose 
far  outweigh  the  drawbacks. 

The  following  table  shows  the  amount  of  cellulose  contained 
in  the  most  important  vegetables  used  as  food  by  man  ;  from  a 
dietetic,  point  of  view  this  is  not  without  interest. 


Pebcentage  of  Cellulose  in  various  Articles  of  Diet  in  a 
Natural  State.'' 

Cellulose.  Water. 

Eice  flour 0.2 13.0 

Wheat  flour  (fine) 0.3 13.0 

Cucumber 0.6 96.0 

Eice 0.6  .....    .  13.0 

Onion 0.7 86.0 

Potato 0.8 7o.O 

Cauliflower 0.9 91.0 

Asparagus 1-0 94.0 

Carrots 1-0 89.0 

Melon 1.1      90.0 

Mushroom 1-4      91.0 

Apple  (including  pips) 1-5 85.0 

Eye  meal 1-6 14.0 

Eadish       1.6 87.0 

Cabbage 1-8 90.0 

Green  peas 1-9      "8.0 

Eye  2.0 15.0 

Strawberries         2.3 88.0 

Maize 2.5 13.0 

Wheat       2.5 14.0 

Peas         ^ 2.6 15.0 

Horseradish.        . 2.8  ......  77.0 

Lentils 3.0  .        .    .  12.0 

Hazel-nut      3.3 3.8 

Beans 3.6 14.0 

Grapes  (including  pips) 3.6 78.0 

Pears  (including  pips)  ....        .      4.3 83.0 

Barlev 5.3  14.0 

Walnut 6.2 4.7 

Almonds        6.6      5.4 

Easpberries   ....  6.7 86.0 


1  G.  Meyer,  ZeitscJir.  f.  Biolog.,  vol.  vii.  pp.  32  and  33 :  1871 ;   compare  also 
Eubner,  Zeitschr.  f.  Biolog.,  vol.  xix.  p.  45  :  1883. 

2  Volt,  Sitzungsber.  der  bayr.  Akad. :  December,  1869. 

3  The  average  figure,  taken  from  König's  work  previously  quoted. 


74 


LECTURE   V 


Percentage  of  Cellulose  in  Dried  Articles  of  Diet. 


Cellulose. 

Rice  flour 0.2 

Wheat  flour  (fine)    .    .    .  0.4 

Eice 0.7 

Eye  meal 1.8 

Eye 2.4 

"Wheat 2.9 

Maize 2.9 

Potato 3.1 

Hazel-nut 3.4 

Lentils 4.1 

Beans 4.1 

Onion 5.0 

Barley 6.2 

Peas 6.4 

Walnut 6.5 

Almond 6.9 


Cellulose. 

Spinach 8.1 

Green  peas 8.7 

Carrot 8.8 

Apples 10.0 

Eadish 12.0 

Horseradish 12.0 

Cauliflower 13.0 

Cucumber     ......  14.0 

Mushroom 16.0 

Asparagus 17.0 

Cabbage 18.0 

Strawberries 19.0 

Melon 22.0 

Pears. 25.0 

Easpberries 47.0 


The  amount  of  carbohydrates  and  fats  required  for  our  daily 
nutrition  cannot  be  determined,  as  they  may  either  replace 
each  other  or  be  replaced  by  proteid.  Experience  has  taught 
us  that  workingmen,  who  are  able  to  obtain  sufficient  food,  eat 
daily  from  50  to  200  grms.  of  fat,  and  from  300  to  800  grms. 
of  carbohydrates,  besides  from  100  to  150  grms.  of  proteid. 
Tables  V.  and  VI.  (p.  67)  show  us  how  we  can  combine  such 
articles  of  nutrition  in  the  most  varied  ways.  The  food  must 
be  more  abundant  in  carbohydrates  in  proportion  to  the  work 
performed  by  the  muscles,  and  more  abundant  in  fat  according 
to  the  lowering  of  the  surrounding  temperature.  Travellers  in 
the  far  north  relate  that  they  were  glad  to  adopt  the  habit,  prev- 
alent among  the  natives  in  those  regions,  of  eating  a  pound  of 
butter  or  oil  in  the  day,  and  that  the  distaste  for  large  quanti- 
ties of  fat  returned  as  soon  as  they  reached  warmer  climates. 
On  the  other  hand  the  negroes  in  the  plantations  of  the  tropics, 
while  doing  the  hardest  muscular  work,  thrive  on  a  dietary 
poor  in  fat,  but  very  rich  in  carbohydrates. 


LECTURE  VI 

THE    ORGANIC    FOOD-STUFFS    (conclusion) THE    ORGANIC  COM- 
POUNDS   OF    PHOSPHORUS CHOLESTERIN 

In  the  previous  chapters  we  have  become  acquainted  with 
those  organic  substances  which,  according  to  the  doctrines  of 
physiology  now  prevailing,  are  requisite  for  the  nutrition  of  man. 
But  they  are  probably  much  more  numerous. 

Certain  phosphorus  compounds  should  also  probably  be 
regarded  as  essential  organic  food-substances  of  man.  In  all 
animal  and  vegetable  tissues,  in  every  cell  we  find  two  complex 
organic  compounds,  which  are  very  rich  in  phosphorus,  the 
LECITHINS  and  the  nucleins. 

The  LECITHINS  are  compounds  which  we  may  regard  as 
having  been  formed  from  the  union  of  one  molecule  of  glycerin 
with  two  molecules  of  a  fatty  acid  (stearic  acid,  palmitic  acid, 
or  oleic  acid)  one  molecule  of  phosphoric  acid  and  one  molecule 
of  cholin,  with  the  loss  of  four  molecules  of  water.^ 

Cholin  is  an  ammonium  base,  the  composition  of  which  is 
accurately  known.  When  heated,  it  splits  up  into  glycol  (ethy- 
lene alcohol)  and  trimethylamin.  Its  synthesis  corresponds  with 
this  decomposition  :  Wurtz  ^  produced  it  by  the  action  of  ethy- 
lene oxide  and  water  on  trimethylamin.  The  formula  of  cholin 
is  therefore — 


N^ 


CH3 

CH3 

CH3 

CH2CH2OH 

OH 


In    the  animal  kingdom  cholin  has,  up   to  the  present  time, 

1  Vide  Diakonow,  Centralbl.  f.  d.  med.  Wissensch.,  Nos.  1,  7,  28 :  1868.  Hoppe- 
Seyler,  Med.  chem.  Unters.,  Ueü  ii.  p.  221:  1867;  and  Heft  iii.  p.  405:  1868; 
Strecker,  Ann.  Chem.  Pharm.,  vol.  cxlviii.  p.  77:  1868;  Hundeshagen,  "Zur 
Synthese  des  Lecithins,"  Inaug.  Dissert. :  Leipzig,  1883;  E.  Gilson,  Zeitschr.  f. 
physiol.  Chem.,  vol.  xii.  p.  585  :  1888. 

2  Wurtz,  Ann.  Chem.  Pharm.,  Suppl.  vi.  pp.  116,  197:  1868.  Compt.  rend., 
vol.  Ixv.  p.  1015:  1867;  and  vol.  Ixvi.  p.  772:  1868.  Compare  Baeyer,  ^nn. 
Chem.  Pharm.,  vol.  cxl.  p.  306  :  1866 ;  and  vol.  cxlii.  p.  322 :  1867. 

75 


76  LECTUßE   VI 

been  found  only  in  lecithin.  It  was  first  obtained  by  Strecker  ^ 
from  the  bile,  which  contains  lecithin,  and  hence  it  was  called 
cholin.  Liebreich  ^  found  it  among  the  products  of  decomposi- 
tion of  phosphorus  compounds  from  nerve  substance  (brain). 
Diakonow  showed  that  it  was  a  product  of  decomposition  of 
lecithin.  In  the  tissues  of  plants  cholin  is  found  in  other  com- 
binations as  well  as  in  lecithin.  In  mustard  seed  there  is  an 
alkaloid  (sinapin)  which,  on  boiling  with  alkalies,  is  resolved  into 
smapic  acid  and  cholin.  Two  alkaloids  have  been  obtained  by 
Schmiedeberg  and  his  pupils^  from  the  fly-fungus  {Amanita 
muscaria) — amanitin  and  muscarin,  the  former  of  which  was 
found  to  be  identical  with  cholin.  The  latter,  a  violent  poison, 
differs  from  amanitin  only  in  possessing  one  more  atom  of 
oxygen.  In  fact,  by  the  action  of  boiling  nitric  acid  on  cholin 
(the  cholin  being  taken  indifferently  from  amanita,  from  the 
lecithin  of  the  brain  or  of  yolk  of  egg,  as  well  as  that  syn- 
thetically produced),  an  alkaloid  containing  one  more  atom 
of  oxygen  was  successfully  obtained,  which  acted  poisonously 
in  a  similar  manner  to  muscarin ;  the  action  on  the  heart  in 
particular  being  alike  in  both  cases.  This  intimate  connection 
between  a  substance  contained  in  every  animal  and  vegetable 
cell  and  a  powerful  poison,  is  a  fact  of  great  interest.  Accord- 
ing to  the  more  recent  researches  of  Boehm,^  however,  the  mus- 
carin artificially  produced  by  oxidation  of  cholin  is  not  identical 
with  the  muscarin  from  the  fly-fungus,  but  is  isomeric  ;  the 
pharmacological  action  is  different.  Boehm  found  cholin  in 
other  fungi,  and  obtained  it  in  large  quantities  from  the  residue 
of  crushed  cotton  seeds  and  beech-nuts. 

Lecithins  have,  in  common  with  fats  to  which  they  are  so 
nearly  allied  in  composition,  the  property  of  solubility  in  alco- 
hol and  ether ;  they  are  also  miscible  in  every  proportion  with 
fats  ;  but  at  the  same  time  they  have  the  power  of  swelling  and 
becoming  slimy  in  water.  For  this  reason  they  appear  pecu- 
liarly adapted  to  aid  in  the  interaction  of  watery  solutions  and 
substances  not  soluble  in  water,  and  to  take  part  in  the  most 
various  chemical  processes  in  the  tissues.  But  at  present  we 
know  absolutely  nothing  about  the  part  which  the  lecithins  may 
play  in  any  of  the  vital  functions. 

''■  Strecker,  Ann.  Chem.  Pharm.,  vol.  cxxiii,  p.  353 :  1862  :  vol.  cxlviii.  p.  76 : 
1868. 

*  Liebreich,  ibid.,  vol.  cxxxiv.  p.  29  :  1865. 

^  Schmiedeberg  a,nd  Koppe,  "  Das  Muskarin,  das  giftige  Alkaloid  des  Fliegen- 
pilzes": Leipzig,  1869 ;  E.  Harnack,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  iv.  p. 
168 :  1875  ;  Schmiedeberg  and  Harnack,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  vi. 
p.  101 :  1876. 

*  Boehm,  Arch.f.  exper.  Path.  u.  Pharm.,  vol.  six.  p.  87 :  1885. 


THE    ORGANIC    FOOD-STUFFS  77 

The  next.question  which  must  occupy  our  attention  is  whether 
the  lecithins  of  our  tissues  are  produced  from  the  lecithins  of 
food,  or  by  synthesis  from  other  materials  such  as  fat,  proteid, 
and  phosphoric  acid.  It  has  been  ascertained  from  experi- 
ments in  Hoppe-Seyler's  laboratory  ^  that,  in  artificial  pan- 
creatic digestion,  the  lecithins  take  up  water  and  readily  split 
up  into  glycerin-phosphoric  acid,  fatty  acids,  and  cholin.  It  is 
not  yet  known  whether  this  decomposition  is  complete  in  the 
case  of  normal  digestion,  or  whether  a  portion  is  absorbed 
undecomposed,  and  if  so  how  large  a  portion ;  whether  only 
the  undecomposed  part,  when  absorbed,  can  be  utilized  in  the 
building  up  of  the  tissues,  or  whether  the  products  of  decom- 
position which  are  absorbed  again  become  united ;  whether 
finally  lecithin  may  also  be  formed  from  other  material.  The 
absorption  of  lecithin  or  of  its  products  of  decomposition  is  in 
any  case  complete  ;  neither  lecithin  nor  glycerin-phosphoric  acid 
can  ever  be  found  in  the  feces.  The  presence  of  lecithin  in 
milk  ^  seems  to  show  how  essential  that  substance  is  in  nutrition. 

The  generic  name  of  nuclein  ^  has  been  bestowed  upon  a 
large  number  of  very  different  organic  phosphorus  compounds, 
which  are  to  be  found  in  all  animal  and  vegetable  tissues, 
being  especially  abundant  in  the  nuclei  of  cells.  The  nucleins 
have  as  yet  been  little  investigated,  and  we  have  no  proof  that 
the  pure  substances  hitherto  isolated  are  chemical  individuals. 
All  are  alike  in  being  insoluble  in  alcohol,  ether,  water,  and 
dilute  mineral  acids,  and  in  being  soluble  in  alkalies.  The 
nucleins  are  acids.  The  phosphorus  is  given  oif  from  them  all 
as  phosphoric  acid  on  boiling  with  water,  and  more  rapidly  so 
on  boiling  with  alkalies  or  acids.  But  the  organic  substances 
which  are  combined  with  the  phosphoric  acid  appear  to  be  of 
very  varying  character,  and  have  been  but  little  investigated. 
Most  nucleins  are  proteid  compounds,  although  a  few  do  not 
contain  proteid.  Many,  on  splitting  up,  produce  xanthin, 
hypoxanthin,  guanin,  and  adenin  ^ — crystalline  compounds  rich 


^S.  Bokay,  Zeitschr.  f.  physiol.  Chem.,  vol.  i.  p.  157:  1877. 

2  TolmatschefF,  Hoppe-Seyler's  3Ied.  chem.  Unters.,  Heft  ii.  p.  272  :  1867. 

^  The  Eucleins  were  first  discovered  and  investigated  by  Miescher  in  the 
nuclei  of  pus-corpuscles,  and  subsequently  in  the  yolk  of  egg  and  salmon-sperm 
(Hoppe-Seyler's  3Ied..  chevi.  Unters.,  Heft  iv.  pp.  441,  502  :  1871 ;  Verhand- 
lungen der  naturforschenden  Gesellschaft  zu.  Bo.sel,  vol.  vi.  p.  138:  1874).  The 
most  recent  and  complete  experiments  on  nucleins  were  made  by  Kossel 
Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  284:  1879;  vol.  iv.  p.  290:  1880;  vol.  v' 
pp.  152,  267:  1881;  "Untersuchungen  über  die  Nucleine":  Strassburg,  1881; 
Zeitschr.  f.  physiol.  Chem.,  vol.  vi.  p.  422  :  1882  ;  vol.  vii.  p.  7  :  1882;  vol. 
x.p.  250:  1886;  vol.  xii.  p.  241  :  1888;  Arch.  f.  Anat.  u.  Physiol.,  p.  181  : 
1891. 

*  Piccard,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  vii.  p.  1714  :  1874. 


78 


LECTURE    VI 


in  nitrogen,  which  we  shall  describe  more  at  length  when  we 
consider  the  chemistry  of  urine.  The  preparations  of  nuclein, 
hitherto  analyzed,  contained  from  3.2  .to  9.6  per  cent,  of 
phosphorus. 

The  nucleins  have  much  the  same  solubilities  as  proteids, 
and  are  found  united  with  these  in  the  same  morphological 
structures,  but  they  can  be  separated  by  artificial  gastric 
digestion  (Lectures  X.  and  XL)  :  the  proteids  are  peptonized  ; 
the  nucleins  on  the  other  hand  are  little  affected  by  the  gastric 
juice.  It  appears  that  the  nucleins  mostly  occur  in  the  tissues, 
not  in  a  free  state,  but  as  compounds  with  proteid  (nucleo- 
albumins),  and  perhaps  also  with  lecithin,  and  that  gastric 
digestion  separates  them  from  these  bodies. 

As  an  example  of  the  percentage  composition  of  nucleins, 
I  may  give  the  following  analyses  of  preparations,  which  were 
to  some  extent  pure.  Since  the  nucleins  have  not  yet  been 
prepared  in  a  crystalline  state,  we  have  no  adequate  guarantee 
of  their  chemical  individuality  or  of  the  purity  of  the  prepara- 
tions. 


Nucleins  prepared  from— 

Carp-Roe.^ 

Yeast  ^ 

Yolk  of  Egg.  2 

I. 

II. 

c 

40.8 

42.1 

48.0 

47.8 

H 

5.4 

6.1 

7.2 

7.2 

N 

16.0 

14.7 

14.7 

12.7 

S 

0.4 

0.55 

0.3 

— 

P 

6.2 

5.19 

2.4 

2.9 

Fe 

— 

0.29 

— 

0.25 

0 

31.3 

31.05 

— 

— 

From  some  of  the  nucleins  the  phosphoric  acid  may  be  split 
off  in  combination  with  part  of  the  organic  radical  as  an  acid 
containing  nitrogen,  but  free  from  sulphur,  which,  following 
Altmann's  suggestion,^  we  may  designate  nucleic  acid.  As 
example  of  such  an  acid  may  be  cited  the  nucleic  acid  split  off 
from  the  nuclein  of  yeast,  to  which  the  formula  C^gHggN^gOgg, 
2P  O^  has  been  given.^ 


*  Kossel,  Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  284  :  1879. 

'^  Bunge,  ibid.,  vol.  ix.  p.  56  :  1885. 

3  G.  Walter,  ibid.,  vol.  xv.  p.  489  :  1891. 

4R.  Altmann,  Du  Bois'  Arch.,  p.  524  :  1889. 

^  Altmann,  loc.  cit. 


THE    ORGANIC    FOOD-STUFFS  79 

In  certain  cells  nucleic  acid  appears  to  occur  in  a  free  state. 
Thus  Miescher  ^  has  prepared  a  nucleic  acid  from  salmon-sperm, 
to  which  he  has  assigned  the  formula  C^'^^J^^JJ^^,  2P2O..  In 
the  heads  of  the  spermatozoa  this  acid  is  combined  with  the 
organic  base,  protamin  (see  Lecture  XIX.),  to  form  a  salt.  In 
the  dried  heads  of  the  spermatozoa  the  nucleic  acid  amounts  to 
60.7  per  cent,  and  the  protamin  to  19.8  per  cent. 

Whether  the  nucleins  of  our  tissues  arise  from  the  nucleins 
of  food  (in  which  case  the  nucleins  would  rank  among  the 
number  of  essential  food-substances),  or  whether  the  nucleins 
are  formed  in  the  body  by  synthesis,  is  a  question  of  great  im- 
portance, about  which  as  little  is  known  as  concerning  the 
mode  in  which  the  lecithins  originate.  The  occurrence  of 
nucleins  in  milk  ^  seems  to  point  to  the  former  supposition  as 
the  correct  one,  whereas  the  slight  digestibility  of  the  nucleins 
would  lead  us  to  the  latter  conclusion.  The  experiments  car- 
ried out  in  Hoppe-Seyler's  laboratory  ^  showed  that  nuclein  is 
as  little  aifected  by  artificial  pancreatic,  as  by  artificial  gastric, 
digestion.  Nuclein  was  found  in  abundance  in  the  feces  of 
dogs.  A  quantitative  determination  of  the  comparative  amounts 
of  nuclein  in  food  and  in  the  feces  has  not  yet  been  made, 
and  it  is  therefore  not  yet  known  whether  the  nucleins  are 
absolutely  indigestible,  or  whether  a  part,  and  if  so  how  much, 
is  absorbed. 

The  following  observation,  made  by  Miescher*  on  Rhine 
salmon,  seems  to  show  that  the  nucleins  as  well  as  the  lecithins 
arise  in  the  animal  body  by  synthesis.  The  salmon  travel  up 
the  river  every  year  from  the  sea  to  spawn  in  the  Upper 
Rhine.  During  the  journey,  the  ovary  grows  from  0.4  to 
19.27  per  cent,  of  the  salmon's  entire  weight.  These  journey- 
ings  last  from  four  to  fourteen  weeks.  During  the  whole  of 
this  time  they  take  no  food ;  the  intestinal  canal  is  always 
found  empty.  The  material  which  goes  to  form  the  ovaries 
can  only  be  produced  by  the  muscles,  which  constitute  the 
bulk  of  the  fish's  weight.  Miescher  showed  by  comparative 
determinations,  made  on  fish  of  equal  size,  that  the  muscles 

1  Miescher,  Arch.  f.  exp.  Path.  ii.  Pharm.,  vol.  xxxvii.  p.  100  :  1896. 

2  Nuclein  was  proved  to  be  a  constitiient  of  milk  by  Lubavin  (Hoppe-Seyler's 
Med.  chem.  Unters.,  Heft  iv.  p.  463  :  1871 ;  Per.  d.  deutsch,  ehem.  Ges.,  vol.  x.  p. 
2237  :  1877  ;  and  vol.  xii.  p.  1021  :  1879).  Hammarsten  showed  that  nuclein  is 
contained  in  milk  as  nucleo-albumin  {Zeitschr.f.physiol.  Chem.,  vol.  vii.  p.  227  : 
1883). 

*  Bokay,  Zeitschr.  f.  physiol.  Chem,,  vol.  i.  p.  157  :  1877. 

•*  Miescher,  "  Statistische  u.  biologische  Beiträge  zur  Kenntniss  vom  Leben 
des  Rheinlachses,"  Separatabdruck  aus  der  schweizerischen  Literatursammlung 
zur  internationalen  Fischerei-Ausstellung  in  Berlin,  p.  183  :  1880 ;  and  Arch.  f. 
Anat.  u.  Physiol.,  Anat.  Abth.,  p.  193  :  1881. 


80  LECTURE    VI 

disappear  in  proportion  as  the  ovaries  develop,  and  that  the 
loss  in  weight  of  the  large  lateral  trunk-muscles  is  sufficient  to 
cover  the  increase  in  weight  of  the  ovaries.  Now  the  ova  are 
very  rich  in  lecithin  and  nuclein  ;  the  muscles  however  are 
poor  in  these  compounds.  But  the  muscles  contain  phosphoric 
acid  in  abundance  in  another  form,  probably  as  potassium  salts, 
loosely  united  with  proteids.  Miescher  therefore  concludes  that 
the  new  compounds  characteristic  of  the  egg  are  formed  from 
the  proteid,  the  fat,  and  the  phosphates  of  the  muscles,  a  pro- 
found chemical  rearrangement  taking  place. 

Perhaps  Cholesterin  also  belongs  to  the  organic  food-stuffs 
essential  to  man.  Like  the  lecithins  and  nucleins,  it  is  a 
normal  constituent  of  all  vegetable  and  animal  tissues  and  of 
milk.^  Here  also  we  do  not  know  whether  Cholesterin  is  formed 
only  in  the  plant,  and  enters  the  animal  body  either  directly  in 
the  form  of  vegetable  food  (in  the  case  of  herbivora),  or  indi- 
rectly (in  the  case  of  Carnivora),  or  whether  it  is  formed  from 
other  material  in  the  animal  body.  Cholesterin  is,  like  lecithins 
and  fats,  insoluble  in  water,  and  soluble  in  ether  and  alcohol, 
but  is  distinguished  from  them  by  its  insolubility  in  boiling 
potash  ;  it  cannot  be  saponified,  as  it  is  not  an  ethereal  salt,  but 
a  monatomic  alcohol  with  the  composition  Cg^H^^OH.  The 
chemical  constitution  of  this  compound  is  not  known. 

We  are  still  in  complete  ignorance  concerning  the  fate  of 
Cholesterin  in  the  organism.  Considerable  quantities  of  Choles- 
terin are  being  continually  turned  out  into  the  intestine  along 
with  the  bile,  but  we  do  not  know  whether  this  Cholesterin  is 
taken  up  preformed  in  the  food  or  whether  it  is  formed  from 
other  substances  by  the  organism  itself.  In  huuaan  feces 
Cholesterin  occurs  modified  as  dihydrocholesterin,  formed  by 
the  addition  of  two  atoms  of  hydrogen  to  the  unsaturated 
Cholesterin  molecule.  This  reduction  product  was  named  by 
its  discoverer,  Bondzynski,^  koprosterin,  and  assigned  the 
formula  Cj^H^^OH.  That  this  process  of  reduction  takes  place 
in  the  intestine  is  rendered  probable  by  the  fact  that  in  dogs, 
with  their  short  gut,  the  Cholesterin  of  the  food  and  of  the  bile 
is  passed  unchanged,  whereas  in  the  long  intestine  of  the 
horse,  Cholesterin  undergoes  a  still  further  reduction,  appearing 
in  the  feces  as  C27H,30H.  It  has  not  yet  proved  possible, 
outside  the  body,  by  means  of  reducing  or  putrefactive  proc- 
esses, to  prepare  the  koprosterin  from  Cholesterin.     Koprosterin 

^  Tolmatscheff,  Hoppe-Seyler's  Med.  chem.  Unters.,  Heft  ii.  p.  272:  1867; 
and  Schmidt-Mülheim,  Pfliiger's  Arch.,  vol.  xxx.  p.  384  :  1883. 

2  St.  Bondzynski,  Ber.  d.  deutsch,  chem.  Ges.,  p.  476  :  1896  ;  Bondzynski  and 
Humnicki,  Zeitschr.  f.  physiol.  Chem.,  vol.  xxii.  p.  396  :  1896. 


THE    ORGANIC    FOOD-STUFFS  81 

differs  from .  Cholesterin  both  in  its  melting-point  and  in  its 
action  on  polarized  light,  being  dextro-rotatory,  while  Choles- 
terin is  levo-rotatory.  Moreover  the  color-reactions  of  kopros- 
terin  differ  from  those  of  Cholesterin. 

We  know  nothing  as  yet  concerning  the  significance  of 
Cholesterin  for  any  vital  functions. 


LECTURE  VII 


THE    IjSTOEGANIC    FOOD-STUFFS 

In  our  previous  remarks  on  alimentary  substances  we  have 
not  given  any  account  of  the  inorganic  materials,  salts  and 
water. 

In  deciding  the  question  of  man's  need  for  inorganic  salts, 
we  must  clearly  distinguish  between  the  growing  and  the  adult 
body.  It  is  evident  that  the  former  requires  a  considerable 
amount  of  inorganic  salts  for  its  development.  The  quality 
and  quantity  needed  may  be  best  seen  from  the  composition  of 
milk.  An  infant  weighing  6  or  7  kgrms.^  takes  about  a  liter 
of  milk  daily.     This  contains — ^ 

KjO 0.78  grm. 

NajO 0.23  " 

CaO , 0.33 

MgO 0.06 

FejOj 0.004  " 

PA 0.47  " 

CI 0.44  " 

It  would  be  very  interesting  to  compare  the  composition 
of  the  ash  of  milk  with  that  of  the  total  ash  of  the  infant.  But 
unfortunately  no  analysis  of  the  total  ash  of  an  infant  has  ever 
been  made.  A  comparative  analysis  of  the  ash  of  dog's 
milk  and  the  total  ash  of  a  sucking  puppy  resulted  in  the 
following  figures,'^  which  I  give  together  with  the  analysis  of 
the  ash  of  blood,  and  another  of  the  total  ash  of  a  young  rabbit 
and  a  kitten  while  being  suckled  : — 

^  This  is  what  an  infant  usually  weighs  in  the  sixth  month.  I  choose  this 
stage  for  the  above  table,  because  the  numbers  are  of  a  suitable  size.  Assuming 
that  the  need  for  inorganic  salts  is  in  proportion  to  the  body-weight,  the  decimal 
point  has  only  to  be  moved  one  figure  to  the  right,  in  order  to  ascertain  the 
amount  required  by  an  adult.  But  these  figures  can  only  be  taken  as  a  maximal 
value.  As  we  shall  see  it  is  probable  that  the  adult  does  not  require  nearly  so 
large  an  amount  of  inorganic  salts. 

2  G.  Bunge,  Zeitschr.  f.  Biolog.,  vol.  x.  p.  316 :  1874. 

3  Bunge,  loc.  cit.,  p.  326;  and  Du  Bois'  Arch.,  p.  539:  1886. 

82 


THE   INORaANIC   FOOD-STUFFS. 


83 


One  hundred  parts  of 

Sucking  young  of  animals. 

Dog's 
milk. 

Dog's 
blood. 

Dog's 
blood 

ash  contain. 

Babbit. 

Dog. 

Cat. 

KjO      

10.8 

8.5 

10.1 

10.7 

3.1 

2.4 

NajO 

6.0 

8.2 

8.3 

6.1 

45.6 

52.1 

CaO 

35.0 

35.8 

34.1 

34.4 

0.9 

2.1 

MgO 

2.2 

1.6 

1.5 

1.5 

0.4 

0.5 

FeA 

0.23 

0.34 

0.24 

0.14 

9.4 

0.12 

P2O5      

41.9 

39.8 

40.2 

37.5 

13.3 

5.9 

CI 

4.9 

7.3 

7.1 

12.4 

35.6 

47.6 

This  table  shows  the  remarkable  fact  that  the  proportion 
of  the  various  inorganic  substances  to  each  other  in  milk,  is 
almost  the  same  as  it  is  in  the  whole  body  of  animals  while 
they  are  being  suckled.  This  correspondence  is  the  more 
remarkable  as  the  quantitative  composition  of  the  inorganic 
residue  of  blood  is  completely  different.  But  the  epithelial 
cells  of  the  mammary  gland  do  not  derive  their  nourishment 
directly  from  the  blood,  but  from  the  lymph  which  has  tran- 
suded from  the  latter ;  and  the  composition  of  the  ash  of  lymph 
differs  much  more.  The  fact  that  the  ash  of  milk  contains 
more  potassium  and  less  sodium  than  the  total  ash  of  the 
suckling  may  be  teleologically  explained  by  the  fact  that,  as  I 
have  proved  by  a  series  of  analyses,^  the  animal  as  it  grows 
always  becomes  richer  in  potassium  and  poorer  in  sodium ; 
this  probably  depends  on  the  relative  increase  of  the  muscles 
which  contain  an  abundance  of  potassium,  and  the  relative 
diminution  of  the  cartilage  which  is  rich  in  sodium.  The 
larger  amount  of  chlorin  in  milk  may  perhaps  be  explained  by 
the  fact  that  the  chlorids  are  useful,  not  only  in  the  construc- 
tion of  the  organs,  but  also  in  the  preparation  of  the  digestive 
secretions,  and  that  those  chlorids  which  have  reached  the  in- 
testine with  the  digestive  secretions  do  not  again  become  com- 
pletely absorbed.  It  appears  also  that  the  chlorids  are  impor- 
tant for  renal  secretion.  The  nitrogenous  products  of  metabolism 
cannot  be  eliminated  simply  in  the  form  of  aqueous  solutions ; 
the  presence  of  chlorids  is  also  necessary.^  This  is  shown  by 
the  fact,  among  others,  that  diuretics  also  increase  the  excretion 
of  chlorin. 

It  follows  that  the  inorganic  constituents  are  all  appropri- 
ated by  the  epithelial  cells  of  the  mammary  gland  from  the 


^  Bunge,  loc.  cit.,  p.  324. 

^  The  chlorids   are    occasionally  absent  from    the  urine  in  certain  febrile 
diseases,  especially  in  pneumonia.    See  Lecture  XXVIII. 


84 


LECTÜEE    VII 


blood-plasma  (which  is  of  a  totally  different  composition),  in  the 
exact  proportion  required  by  the  young  animal  for  its  develop- 
ment into  an  organism  like  that  of  the  parent. 

This  fact  alone  refutes  all  previous  attempts  at  a  mechanical 
explanation  of  the  activity  of  the  glands.  It  cannot  be  objected 
that  the  secretion  of  milk  does  not  correspond  with  the  compo- 
sition of  the  sucking  animal,  but,  on  the  contrary,  that  the  tis- 
sues of  the  latter  are  built  up  in  accordance  with  the  composition 
of  the  milk  ;  for  the  incinerated  puppies  were  only  four  days 
old,  and  were  therefore  born  with  an  ash  of  a  composition  cor- 
responding to  that  of  the  ash  of  the  milk.  We  also  find  a  simi- 
lar composition  of  the  total  ash  as  far  down  as  the  lower  verte- 
brates, which  have  no  mammary  glands. 

We  now  know  exactly  what  salts  are  required  by  the  grow- 
ing animal,  and  in  what  proportion  each  must  be  introduced. 
We  may  now  therefore  ask  whether  the  child,  in  passing  from 
milk  to  another  form  of  diet,  will  continue  to  obtain  these  inor- 
ganic salts  in  sufficient  quantities.  In  answer  to  this  question, 
I  give  the  following  table  containing  the  most  reliable  determi- 
nations of  the  constituents  of  the  ash  of  the  most  important 
articles  of  diet,  together  with  analyses  of  the  ash  of  milk. 
The  articles  of  diet  are  arranged  according  to  the  ratio  of  lime 
contained : — 

In  One  Hundeed  Pakts  of  Deied  Substance  the  Peopoetions  aee — 


K^O. 

Na^O. 

CaO. 

MgO. 

Fe,03. 

P.O.. 

01. 1 

Beef 

1.66 

0.32 

0.029 

0.152 

0.02 

1.83 

0.28 

Wheat  .    .    . 

0.62 

0.06 

0.065 

0.24 

0.026 

0.94 

(?) 

Potato  .    .    . 

2.28 

0.11 

0.100 

0.19 

0.042 

0.64 

0.13 

Egg-albumin  .    . 

1.44 

1.45 

0.130 

0.13 

0.026 

0.20 

1.32 

Peas  .    . 

1.13 

0.03 

0.137 

0.22 

0.024 

0.99 

(?) 

Human  milk    . 

0.58 

0.17 

0.243 

0.05 

0.003 

0.35 

0.32 

Yolk  of  egg    .    . 

0.27 

0.17 

0.380 

0.06 

0.040 

1.90 

0.35 

Cow's  milk      .    . 

1.67 

1.05 

1.51 

0.20 

0.003 

1.86 

1.60 

The  above  table  shows  that  the  other  articles  of  food  possess 
all  the  inorganic  constituents  in  as  large  or  in  a  larger  quan- 
tity than  milk.  Lime  is  the  only  inorganic  material  which  we 
have  to  provide  for  in  the  choice  of  a  child's  food.  If  brought 
up  on  meat  and  bread  a  child  would  probably  not  obtain  the 
lime  requisite  for  the  growth  of  its  frame.  The  leguminosae 
contain  more ;  but  the  only  food  which  has  the  same  amount 

'  The  amount  of  chlorin  in  cereals  and  leguminosse  has  never  yet  been  cor- 
rectly determined,  too  low  an  estimate  having  been  formed.  Concerning  this, 
see  Behaghel  von  Adlerskron,  Zeitschr.f.  analyt.  Chem.,  vol.  xii.:  1873. 


THE   INORGANIC    FOOD-STUFFS  85 

as  milk  is  the  yolk  of  egg,  which  should  therefore  always  be 
given  to  children  when  milk  is  either  not  procurable  or  cannot 
be  digested.  Considerable  quantities  of  lime  occur  in  spring- 
water,  but  it  is  not  known  whether  these  are  assimilated.  Lime 
is  found  combined  with  organic  substances  in  food ;  it  is  there- 
fore irrational  to  prescribe  lime  for  children  in  the  form  of  in- 
organic compounds.  In  medical  practice,  rickety  children  are 
constantly  being  ordered  a  couple  of  teaspoonfuls  of  lime-water. 
This  is  useless,  because  the  amount  ordered  is  far  too  small.  A 
saturated  solution  of  lime  contains  less  lime  than  cow's  milk. 
In  a  pint  of  cow's  milk  I  found  1.7  grm.  CaO  ;  a  pint  of  lime- 
water  contains  only  1.3  grm.  CaO. 

The  nature  and  causes  of  rickets  are  still  quite  unknown. 
It  is  a  fact  that  artificial  feeding  of  growing  animals  on  a  diet 
containing  a  little  lime  can  produce  a  diminution  of  the  salts  of 
lime  in  the  bones,  rendering  them  abnormally  pliable  and 
brittle.  It  is  also  affirmed  that  in  several  experiments  of  this 
nature  true  rickets  has  been  produced  with  all  the  characteristics 
of  this  disease.^  But  it  is  equally  a  fact  that  children  become 
rickety  who  have  never  suffered  from  want  of  lime  in  their 
food.  In  these  cases  it  seems  obvious  to  suppose  that,  owing 
to  disturbed  digestion,  the  lime  salts  have  not  been  adequately 
absorbed ;  ^  or  that,  in  spite  of  adequate  absorption,  they 
have  not  been  assimilated  owing  to  abnormal  processes  in 
the  bone-forming  tissues.  All  speculation  on  the  truth  of 
either  theory  is  quite  useless,  until  we  have  careful  and  reli- 
able experiments  on  the  metabolism  of  rickety  children  com- 
pared with  that  of  healthy  ones  of  the  same  age,  and  brought  up 
on  the  same  food.  In  spite  of  much  experimental  work  on  the 
subject,  all  attempts  to  give  a  satisfactory  explanation  of  the 
causation  of  osteomalacia  have  been  as  unsuccessful  as  in  the 
case  of  rickets.^ 

Finally,  the  above  table  shows  that  cow's  milk,  compared 
with  organic  food-stuffs,  is  much  richer  in  inorganic  salts  than 

^  Erwin  Voit,  Zeitschr.  f.  Biolog.,  vol.  xvi.  p.  55  :  1880.  An  account  of  the 
previous  literature  will  also  be  found  here.  See  further,  A.  Baginsky,  Virchow's 
Arch.,  vol.  Ixxxvii.  p.  301 :  1882;  and  Seemann,  Zeitschr.  f.  klin.  Med.,  vol.  v. 
pp.  1,  152  :  1882. 

2  In  the  researches  on  the  absorbability  of  calcium  compounds  we  meet  with 
the  same  difficulty  as  in  the  case  of  the  iron  compounds  (see  Lect.  XXV.):  the 
greater  part  of  the  lime  is  excreted  through  the  intestines,  only  a  small  propor- 
tion finding  its  way  into  the  urine.  On  this  point  compare  Fr.  Voit,  Zeitschr.  f. 
Biolog.,  vol.  xxix.  p.  325 :  1893.  Here  also  will  be  found  an  account  of  the 
earlier  work  on  the  subject.  Compare  also  Rudel,  Arch.  f.  exper.  Path.  u.  Pharm., 
vol.  xxxiii.,  pp.  80  and  90, 1893. 

^  H.  Stilling  and  J.  v.  Mering,  Centralbl.  f.  d.  med.  Wissensch.,  p.  803  : 
1889 ;  L.  Gelpke,  "  Die  Osteomalacic  im  Ergolzthale  "  :  Basel,  1891. 


86  LECTURE    VII 

human  milk.  This  may  be  teleologically  explained  by  the  fact 
that  the  calf  grows  much  more  rapidly  than  the  infant.  It  is 
therefore  probable  that  the  adult  organism  could  exist  with  a 
very  small  amount  of  salts ;  m  fact,  it  is  ä  priori  difficult  to 
see  what  the  constant  addition  of  salts  is  required  for.  In- 
organic salts  serve  a  totally  different  purpose  to  the  organic 
food-stuffs.  The  latter  act  as  sources  of  energy ;  chemical 
potential  energy  is  introduced  with  them  into  our  tissues,  and 
is  converted  by  the  decomposition  and  oxidation  of  these  or- 
ganic substances  into  all  those  forms  of  kinetic  energy  which 
make  up  life  as  understood  by  our  senses.  They  serve  us  by 
the  very  fact  of  their  decomposition.  The  necessity  for  their 
constant  renewal  is  not  only  a  matter  of  experience ;  it  is  also 
at  once  apparent  on  ä  j)riori  grounds.  Inorganic  salts  must  be 
regarded  from  a  different  point  of  view.  These  are  already 
saturated  compounds  of  oxygen,  or  chlorids,  which  likewise 
have  no  affinity  for  oxygen.  No  energy  is  set  free  in  the 
body  by  their  decomposition  and  oxidation ;  they  can  in  no 
way  become  used  up  and  useless.  Why  therefore  are  they 
renewed  ?  Even  water  behaves  differently  to  the  salts  ;  it  as- 
sists in  the  elimination  of  the  waste  products  of  metabolism. 
The  kidneys  can  only  separate  the  nitrogenous  substances 
when  in  a  watery  solution.  The  diffusion  of  gases  in  the 
lungs  is  only  possible  while  the  surface  of  the  lungs  is  moist. 
The  expired  air  is  saturated  with  watery  vapor.  The  evapo- 
ration of  water  from  the  surface  of  the  skin  plays  a  most  im- 
portant part  in  regulating  the  heat  of  the  body.  The  ä  priori 
necessity  for  a  constant  supply  of  water  is  thus  likewise  evi- 
dent. But  it  is  otherwise  with  the  salts.  It  is  conceivable 
that  if  only  the  organic  aliments  and  water  always  entered  the 
organism  in  sufficient  quantity,  the  inorganic  salts  arising  from 
the  decay  of  the  tissues  might  again  be  used  in  the  reconstruc- 
tion of  the  tissues.  Even  if  a  little  waste  were  unavoidable,  as 
by  excretion  with  the  feces  in  consequence  of  incomplete  ab- 
sorption of  the  gastric  juices,  by  the  scaling  off  of  the  epidermis, 
the  loss  of  hair,  &c.,  yet  we  might  expect  that  the  full-grown 
organism  would  cling  firmly  to  its  store  of  salts,  and  would  re- 
quire but  a  very  small  additional  supply.  The  constant  supply 
of  salts  in  considerable  quantities  is  not  an  ä  priori  necessity 
for  the  adult. 

We  must  therefore  determine  the  question  by  experiment. 
We  might  feed  a  full-grown  animal  for  a  long  period  exclu- 
sively on  organic  food-stuffs  and  water,  and  ascertain  the  dis- 
turbances that  would  occur,  and  the  length  of  time  it  would  live 
on  such  a  diet.     This  fundamental  experiment  in  metabolism  had, 


THE    INORGANIC    FOOD-STUFFS  87 

until  quite  recently,  only  once  been  made  by  Forster,  Voit's 
assistant  in  Munich.^ 

Forster  met  with  insuperable  difficulties  when  he  tried  to 
obtain  food  free  from  ash.  It  is  possible  to  get  carbohydrates 
and  fats  free  from  ash,  but  no  one  has  yet  succeeded  in 
separating  proteid  from  all  inorganic  matter.  Even  crystal- 
line proteid  contains  all  the  constituents  of  ash  in  small 
quantity.  Forster,  in  his  experiments,  employed  the  residue 
of  the  meat  left  from  the  preparation  of  Liebig's  extract  of 
meat.  After  boiling  it  repeatedly  with  distilled  water  and 
drying,  it  still  contained  0.8  per  cent,  of  ash.  Forster  fed  two 
dogs  on  this  proteid  containing  this  small  amount  of  salts,  as 
well  as  on  fat,  sugar,  and  starch-flour.  He  also  fed  three 
pigeons  on  starch-flour  and  casein,  which  likewise  contained 
very  little  saline  ingredient. 

Forster  observed  that  the  animals  died  remarkably  quickly 
when  fed  on  this  diet.  The  three  pigeons  lived  thirteen, 
twenty-five,  and  twenty-nine  days.  One  of  the  dogs  was  "  so 
ill  at  the  end  of  thirty-six  days  that  he  would  certainly  have 
died  in  a  short  time  if  the  experiment  had  been  continued, 
while  the  other  was  dying  at  the  end  of  twenty-six  days." 
When  completely  deprived  of  food,  dogs  live  from  forty  to 
sixty  days.  Food  from  which  the  organic  salts  have  been  re- 
moved appears  to  be  more  rapidly  fatal  than  the  deprivation  of 
all  food. 

Forster  concludes,  from  these  experiments,  that  the  full- 
grown  animal  requires  considerable  quantities  of  inorganic 
salts.  An  objection  may  however  be  raised  to  this  conclusion, 
for  there  is  one  condition  to  which  Forster  has  omitted  to  draw 
attention — I  mean  the  formation  of  free  sulphuric  acid  from 
the  sulphur  of  the  proteid. 

Proteid  contains  from  J  to  1 J  per  cent,  of  sulphur  which, 
in  the  decomposition  and  oxidation  of  proteid,  is  converted  into 
sulphuric  acid.  Eighty  per  cent,  of  the  sulphur  taken  in  food 
appears  in  this  form  in  the  urine.  Under  normal  conditions 
this  sulphuric  acid  is  united  with  the  bases  which  are  taken  up 
with  every  form  of  animal  and  vegetable  food.  Animal  food 
contains  basic  phosphates  of  the  alkalies,  carbonates  of  the 
alkalies,  and  alkali-albuminates ;  vegetable  food  yields  in  addi- 
tion the  alkaline  salts  of  vegetable  acids,  such  as  tartaric,, 
citric,  malic,  &c.,  which  in  the  organism  are  converted  into 
carbonates  by  oxidation.  These  bases  saturate  the  sulphuric 
acid  formed  from  proteid.  If  the  basic  salts  are  removed  from 
the  food,  this  powerful  acid  finds  no  bases  at  hand  to  neutralize 

■'J.  Forster,  Zeitschr.f.  Biolog.,  vol.  is.  p.  297:  1873. 


88  LECTURE    VII 

it,  and  consequently  attacks  those  bases  which  are  integral 
constituents  of  the  living  tissues ;  figuratively,  it  may  be  said 
to  wrench  individual  bricks  out  of  their  places,  and  thus  to 
induce  the  destruction  of  the  edifice,^  This  appears  to  me  to 
be  the  cause  of  the  rapid  death  in  the  animals  experimented 
upon  by  Forster.  The  remarkable  fact  that  the  dogs  died  in  a 
shorter  time  than  when  simply  starved,  would  be  explicable  on 
this  ground.^  The  correctness  of  this  reasoning  has  been  tested 
experimentally  by  Lunin.^ 

Lunin  fed  a  certain  number  of  his  animals  with  food  de- 
prived of  its  mineral  constituents ;  the  others  were  treated  in  a 
similar  way,  but  with  an  addition  of  carbonate  of  soda  which 
was  just  sufficient  to  neutralize  the  sulphuric  acid  formed  from 
the  sulphur  of  the  proteid. 

It  was  important  to  use  as  large  a  number  of  animals  as 
possible,  in  order  to  eliminate  the  influence  of  accidental 
factors  and  thus  arrive  at  a  reliable  result.  Mice  were  there- 
fore chosen  for  the  purpose,  since  it  would  have  been  almost 
impossible  to  obtain  food  free  from  mineral  constituents  in  the 
quantity  requisite  for  a  number  of  large  animals. 

The  food  was  prepared  in  the  following  manner.  By  pre- 
cipitating diluted  milk  with  acetic  acid,  and  washing  the  finely 
flocculent  coagulum  with  water  acidified  with  acetic  acid,  a 
mixture  of  fat  and  casein  was  obtained,  which  only  contained 
from  .05  to  .08  of  ash  in  100  parts  of  dry  matter,  therefore  ten 
times  less  salts  than  in  the  experiments  of  Forster.  To  this 
mixture,  cane  sugar  deprived  of  its  ash  was  added  as  a  repre- 
sentative of  the  third  group  of  food-stuffs. 

On  this  food  and  distilled  water,  five  mice  lived  eleven, 
thirteen,  fourteen,  fifteen,  and  twenty-one  days.  Two  mice 
that  were  completely  starved,  lived  four  days  :  two  more  only 
three  days. 

Again,  six  mice  were  fed  upon  the  same  food  with  the 
addition  of  carbonate  of  soda.  These  lived  sixteen,  twenty- 
three,  twenty-four,  twenty-six,  twenty-seven,  and  thirty  days, 
therefore  twice  as  long  as  the  animals  which  had  no  base  to 
saturate  the  sulphuric  acid  formed. 

^  As  we  shall  see  later  on  {vide  Lecture  XIX.),  the  organism  of  the  dog  is 
able  to  protect  itself  against  the  injurious  action  of  free  acids,  by  splitting  off 
ammonia  from  the  nitrogenous  organic  compounds.  But  this  power  is  not 
unlimited,  and  it  is  doubtful  whether  the  ammonia  is  invariably  present  in  the 
particular  cells  in  which  the  sulphuric  acid  thus  liberated  begins  its  work  of 
destruction. 

2  G.  Bunge,  Zeitschr.  f.  Biolog.,  vol.  x.  p.  130:  1874. 

3  N.  Lunin  (Bunge's  laboratory),  "  Ueber  die  Bedeutung  der  anorganischen 
Salze  für  die  Ernährung  des  Thieres,"  Dissert.:  Dorpat,  1880.  Reprinted  in 
Zeitschr.  f.  physiol.  Chem.,  vol.  v.  p.  31 :  1881. 


THE    INORGANIC    FOOD-STUFFS  89 

It  might  be  objected  that  the  animals  lived  longer,  not  be- 
cause of  the  neutralization  of  the  sulphuric  acid,  but  because 
they  obtained  at  least  one  inorganic  ingredient.  This  objection 
is  answered  by  the  following  experiment,  in  which  seven  mice 
were  given,  ceteris  paribus,  instead  of  the  carbonate  of  soda,  an 
equivalent  quantity  of  chlorid  of  sodium — that  is,  a  neutral 
salt  incapable  of  neutralizing  the  sulphuric  acid.  The  seven 
mice  expired  after  six,  ten,  eleven,  fifteen,  sixteen,  seventeen, 
and  twenty  days.  In  this  case,  although  they  received  two  in- 
organic substances,  sodium  and  chlorin,  they  lived  only  half  as 
long  as  the  animals  which  received  but  one,  sodium,  and  in  fact 
no  longer  than  the  animals  which  had  no  inorganic  addition  at 
all.  The  experiments  were  in  complete  accordance  with  my 
deductions.  As  a  control,  two  parallel  series  of  experiments 
with  potassium  chlorid  and  potassium  carbonate  were  carried 
out,  and  gave  precisely  the  same  results. 

By  preventing  the  formation  of  free  sulphuric  acid,  the 
animals  lived  twice  as  long,  but  still  for  a  very  short  period.  As 
the  action  of  the  acid  could  not  have  caused  their  death,  what 
made  the  mice  die  ?  Was  the  composition  of  the  organic  food- 
stuffs insufficient?  In  order  to  decide  this  question,  all  the 
inorganic  salts  of  milk  were  added  to  the  same  artificial  mixture 
of  organic  food,  in  the  exact  proportions  in  which  they  exist 
in  the  ash  of  milk,  and  in  the  same  relation  to  the  amount  of 
organic  matter  as  in  milk.  Six  mice  lived  twenty,  twenty-three, 
twenty-three,  twenty-nine,  thirty,  and  thirty-one  days  upon  this 
mixture — no  longer  than  they  did  with  the  carbonate  of  soda 
only.  Of  three  mice  which  were  fed  exclusively  on  cow's  milk, 
one  died  after  forty-seven  days,  and,  as  dissection  showed,  of  in- 
tussusception (compare  p.  72)  ;  the  two  others  lived  in  their 
cage  for  two  and  a  half  months,  grew  considerably  fatter,  and 
were  in  capital  condition  when  the  experiment  ceased. 

It  is  a  noteworthy  fact  that,  although  animals  can  live  on 
milk  alone,  yet  if  all  the  constituents  of  milk  which  according 
to  the  present  teaching  of  physiology  are  necessary  for  the 
maintenance  of  the  organism  be  mixed  together,  the  animals 
rapidly  die.  Cannot  cane  sugar  take  the  place  of  sugar  of 
milk  ?  Or  are  the  inorganic  and  organic  constituents  of  milk 
chemically  combined,  and  only  assimilable  in  this  combination  ? 
On  precipitation  of  the  casein  by  acetic  acid,  the  small  amount 
of  proteid  in  the  milk  remained  in  solution.  Cannot  this 
proteid  be  replaced  by  the  casein  ?  Or  does  milk  contain,  in 
addition  to  proteid,  fat,  and  carbohydrates,  other  organic  sub- 
stances, which  are  also  indispensable  to  the  maintenance  of  life? 
It  would  be  worth  while  to  continue  the  experiments. 


90  LECTURE   VII 

The  question  as  to  the  need  of  adult  anunals  for  inorganic 
salts  cannot  be  considered  as  settled.  Before  it  can  be  decided, 
we  must  become  intimately  acquainted  with  all  the  organic 
food-stuffs  Avhich  are  indispensable ;  we  must  also  manage  to 
combine  them  in  such  a  way  that  they  may  be  palatable  to  the 
animals  during  lengthened  experiments.  Finally,  we  must  be 
able  to  saturate  the  sulphuric  acid  resulting  from  the  proteid — 
by  means  of  a  harmless  organic  base,  such  as  cholin — without 
the  addition  of  inorganic  bases.  But  even  then  it  would  prob- 
ably be  impossible  to  come  to  a  decision,  because  it  is  beyond 
our  power  to  ensure  the  presence  of  the  base  at  the  spot  where 
the  sulphuric  acid  is  set  free,  or  because  the  sulphates,  formed 
with  the  base  thus  artificially  introduced,  expel  the  normal  salts 
from  the  tissues.  The  difficulty  appears  for  the  present  to  be 
insuperable. 

There  is  only  one  inorganic  salt  about  which  I  must  add  a 
few  words,  because  it  holds  a  rather  exceptional  position — com- 
mon salt. 

It  is  a  very  remarkable  fact  that  of  all  the  inorganic  salts 
in  our  bodies  we  only  take  one  with  our  organic  food-stuffs, 
and  that  is  common  salt.  We  obtain  enough  of  all  the  other 
salts  from  the  amount  contained  in  our  food,  and  we  never 
think  of  providing  ourselves  with  them  separately.  Common 
salt  forms  the  only  exception,  which  is  the  more  remarkable  as 
our  diet  is  by  no  means  deficient  in  it.  All  vegetable  and 
animal  food  contains  considerable  quantities  of  chlorin  and 
sodium.  Why  do  these  quantities  not  suffice,  and  why  do  we 
add  common  salt? 

In  the  earlier  experiments  made  to  decide  this  point,  one 
fact  was  quite  overlooked,  which  appears  to  me  likely  to  lead 
to  a  correct  solution  of  the  difficulty.  I  mean  the  fact  that 
the  desire  for  salt  in  the  food  was  only  observed  in  the  case 
of  herbivora,  and  never  in  the  case  of  Carnivora.  Our  car- 
nivorous domestic  animals,  the  dog  and  the  cat,  prefer  unsalted 
to  salted  food,  and  show  great  dislike  to  very  salt  food,  while 
the  domesticated  herbivora  are  well  known  to  be  very  fond  of 
salt.  The  same  thing  has  been  observed  in  wild  animals.  It 
is  a  known  fact  that  wild  ruminants  and  hoofed  animals  seek 
out  salt-rocks  and  pools,  and  places  where  salt  effloresces,  to  lick 
the  salt,  and  that  hunters  watch  for  them  at  such  places,  or 
expose  salt  as  a  bait.  This  has  been  noticed  by  numerous 
travellers  to  hold  good  for  herbivora  of  all  countries  and  climates, 
but  it  has  never  been  observed  in  the  case  of  beasts  of  prey. 

The  difference  is  the  more  striking  as  the  amount  of  salt 
which  herbivorous  animals  take  in  with  their  food  is,  compared 


THE    INOEGANIC    FOOD-STUFFS  91 

with  the  weight  of  the  body,  generally  not  much  less  than  that 
consumed  by  carnivorous  animals.  On  the  other  hand  there  is 
a  considerable  difference  in  another  constituent  of  the  ash  of 
their  food,  in  the  potassium.  Herbivorous  animals  take  at 
least  three  or  four  times  as  much  of  salts  of  potassium  as  the 
Carnivora.  This  fact  leads  me  to  imagine  that  the  abundance 
of  potassium  in  vegetable  food  is  the  cause  of  the  need  for  salt 
in  the  herbivora. 

If,  for  instance,  a  salt  of  potassium,  such  as  potassium 
carbonate,  meets  with  common  salt  or  chlorid  of  sodium  in 
solution,  a  partial  exchange  takes  place ;  chlorid  of  potassium 
and  carbonate  of  sodium  are  formed.  Now  chlorid  of  sodium 
is  well  known  to  be  the  chief  constituent  among  the  inorganic 
salts  of  blood-plasma.  When,  therefore,  salts  of  potassium 
reach  the  blood  by  the  absorption  of  food,  an  exchange  takes 
place.  Chlorid  of  potassium  and  the  sodium  salt  of  the  acid 
which  was  combined  with  the  potassium  are  formed.  Instead 
of  the  chlorid  of  sodium,  therefore,  the  blood  now  contains 
another  sodium  salt,  which  did  not  form  part  of  the  normal  com- 
position of  the  blood,  or  at  any  rate  not  in  so  large  a  proportion. 
A  foreign  constituent  or  an  excess  of  a  normal  constituent,  i.  e., 
sodium  carbonate,  has  arisen  in  the  blood.  But  the  kidneys 
possess  the  function  of  maintaining  the  same  composition  of  the 
blood,  and  of  thus  eliminating  every  abnormal  constituent  and 
any  excess  of  a  normal  constituent.  The  sodium  salt  formed  is 
therefore  ejected  by  the  kidneys,  together  with  the  chlorid  of 
potassium,  and  the  blood  becomes  poorer  in  chlorin  and 
sodium.  Common  salt  is  therefore  withdrawn  from  the  or- 
ganism by  the  ingestion  of  potassium  salts.  This  loss  can  only  be 
made  up  from  without,  and  this  explains  the  fact  that  animals, 
which  live  on  a  diet  rich  in  potassium,  have  a  longing  for  salt. 

I  have  proved  the  correctness  of  this  deduction  by  experi- 
ment. To  a  diet  of  uniform  character  salts  of  potassium  were 
one  day  added,  the  consequence  being  a  striking  increase  in 
the  excretion  of  chlorin  and  sodium.  I  have  tried  this  experi- 
ment on  myself  with  all  the  salts  of  potassium  which  are 
concerned  in  human  nutrition.  Eighteen  grammes  K,0,  as 
phosphate  or  citrate,  divided  into  three  doses  during  the  day, 
caused  a  loss  to  the  body  of  6  grms.  of  common  salt,  besides  2 
grms.  of  sodium ;  for  the  potassium  salts  effect  an  exchange, 
not  only  with  the  chlorid,  but  also  with  other  compounds  of 
sodium,  as  albuminate,  carbonate,  and  phosphate. 

The  amount  of  potassium  taken  in  these  experiments  was 
not  large — in  fact,  much  less  than  that  introduced  with  the 
most  important  vegetable  articles  of  diet ;  and  yet  6  grms.  of 


92  LECTURE    VII 

salt  were  withdrawn  from  the  organism  by  it.  This  is  about 
one-half  of  the  common  salt  which  is  contained  in  the  5  liters 
of  a  man's  blood.  That  other  tissues  likewise  suffer  by  this 
loss  is  undoubted.  But  in  the  first  instance  the"!  blood  is 
chiefly  affected,  and  I  think  that  if  this  loss  in  the  blood  was 
covered  by  a  comparatively  small  loss  in  the  other  tissues,  a 
fresh  addition  of  potassium  must  have  the  effect  of  producing 
a  fresh  loss  of  sodium.  Experiments  of  this  kind  have  not 
so  far  been  made.  It  has  not  yet  been  ascertained  up  to 
what  point  the  body  will  continue  to  give  up  sodium,  when 
potassium  is  constantly  taken.  There  is  no  doubt  that  a 
point  would  soon  be  reached  at  which  the  body  would  stoutly 
retain  its  remaining  sodium. 

But  even  those  quantities  of  chlorin  and  sodium,  the 
loss  of  which  I  have  specially  investigated,  appear  to  me 
sufficiently  large  to  account  for  the  need  to  replace  them 
caused  by  eating  vegetables  containing  an  abundance  of  potas- 
sium. Having  regard  to  the  important  part  which  salt  plays 
in  the  organism  (as  in  the  formation  of  the  digestive  secretion, 
or  in  dissolving  the  globulins),  even  a  small  diminution  may  be 
prejudicial  to  certain  functions,  and  may  give  rise  to  the  need  of 
recovering  the  loss. 

As  already  mentioned,  the  amount  of  potassium  taken  in 
my  experiments  was  not  more  than  18  grms.  A  man  who 
lives  chiefly  on  potatoes  takes,  in  the  course  of  the  day,  up 
to  40  grms.  of  potassium.  This  shows  why  potatoes  are  so 
unpalatable  without  salt,  and  are  eaten  everywhere  with  well- 
salted  adjuncts.  Like  potatoes,  all  the  other  important  vege- 
table articles  of  diet,  the  cereals  and  leguminosse,  are  very  rich 
in  potassium,  and  this  explains  the  fact  that  country  people,  liv- 
ing mainly  on  a  vegetable  diet,  use  more  salt  than  the  inhabi- 
tants of  towns,  who  eat  a  great  deal  of  animal  food.  It  has 
been  statistically  shown  in  France  that  people  living  in  the 
country  eat  three  times  as  much  salt  per  head  as  those  in  towns. 

We  may  now  ask  what  the  people  do  who  take  no  vegetable 
food  at  all.  There  are  whole  tribes  of  hunters,  fishermen,  and 
other  nomads,  who  live  entirely  on  animal  food.  We  might 
expect  that  these  people  would,  like  the  carnivorous  animals, 
have  a  disinclination  for  salt.  This  is  in  fact  the  case.  In 
order  to  ascertain  this,  I  have  gone  through  a  very  large 
number  of  works  of  travel,  and  have  obtained  a  great  deal  of 
information  from  recent  travellers,  either  personally  or  by 
letter.  From  all  this  it  appears  to  be  a  universal  rule  that  in 
all  times  and  in  all  lands  those  people  who  live  entirely  upon 
animal  food  either  have  never  heard  of  salt,  or,  if  they  possess 


THE    INOEGANIC    FOOD-STUFFS  93 

it,  avoid  it ;  .  whereas  the  people  whose  staple  food  is  vegetable 
have  the  greatest  desire  for  it,  and  regard  it  as  an  indispensable 
article  of  diet. 

This  difference  was  manifested  as  far  back  as  the  ancient 
Greek  and  Roman  times,  when  the  sacrificial  animals  were 
always  offered  to  the  gods  without  salt,  but  the  fruits  of  the 
earth  with  salt.  The  Mosaic  law  expressly  commanded  the 
Jews  to  present  their  vegetable  offerings  accompanied  by  salt 
to  their  Deity.^ 

The  Indo-Germanic  languages  have  no  common  word  for 
salt,  just  as  they  have  none  for  farming  industries,  whereas 
the  terms  used  in  cattle-breeding  may  mostly  be  traced  back 
to  common  roots.  This  probably  shows  that  the  Indo-Ger- 
manic tribes  knew  nothing  about  salt  so  long  as  they  were 
wandering  about — an  undifferentiated  nation — pasturing  their 
flocks  on  the  summit  and  slopes  of  the  mighty  Bulur-Tagh. 
They  first  became  acquainted  with  it  after  their  dispersion, 
when  they  began  farming  and  took  to  vegetable  food.  In 
the  time  depicted  by  Tacitus,  we  find  the  Germans  just 
adopting  fixed  places  of  abode,  and  beginning  to  devote 
themselves  to  agriculture.  But  at  this  time  they  did  not 
know  how  to  obtain  a  regular  supply  of  salt,  although  the 
desire  for  it  was  already  awakened  in  them,  since  Tacitus  gives 
accounts  of  raging  and  decimating  wars,  which  were  carried  on 
by  different  tribes  for  the  possession  of  the  salt-mines  on  the 
frontiers. 

The  Finnish  languages  have  up  to  the  present  day  no  word 
for  salt.  The  western  Finlanders,  who  are  now  engaged  in 
farming,  use  salt  and  call  it  by  the  German  name.  On  the 
other  hand  the  eastern  Finlanders,  who  still  lead  hunters'  and 
nomads'  lives,  use  no  salt  whatever,  and  this  is  the  case  with 
all  the  other  hunting,  fishing,  and  nomadic  tribes  in  the  north 
of  Eussia  and  in  Siberia.  It  is  not  because  they  are  un- 
acquainted with  salt,  or  cannot  procure  it,  but  because  they 
have  a  decided  dislike  to  it.  In  all  parts  of  Siberia  there 
are  rock-salt  strata,  salt  lakes,  and  salt  efilorescences.  The 
Siberian  hunters  are  only  interested  in  these  salt  strata  be- 
cause the  flocks  of  reindeer  assemble  in  these  places  to  lick  the 
salt ;  the  hunters  themselves  devour  their  meat  without  it.  A 
large  number  of  Siberian  travellers  have  informed  me,  both 
personally  and  by  letter,  that  such  is  the  case  with  all 
the  Siberian  tribes.      The  mineralogist,  C.  von  Ditmar,  who 

^  The  sources  of  these  and  all  following  statements  concerning  the  use  of 
salt  among  different  nations  are  quoted  in  my  work,  "  Ethnologischer  Nachtrag 
zur  Abhandlung  über  die  Bedeutung  des  Kochsalzes,  u.  s.  w.,"  Zeitschr.  f.  Biolog. , 
vol.  X.  p.  111 :  1874. 


94  LECTURE   VI! 

travelled  over  the  whole  of  Siberia  between  1851  and  1856, 
and  lived  for  a  long  time  among  the  Kamtschadales,  writes  to 
me  as  follows  :  "  I  have  frequently  in  my  travels,  given  those 
people  (Kamtschadales,  Korachs,  Tschuktsches,  Ainos,  Tun- 
guses)  some  of  my  salted  viands  to  taste,  and  have  noticed  the 
grimaces  they  made,  showing  how  much  they  disliked  it." 
Ditmar  relates  how  the  Kamtschadales  live  chiefly  on  fish, 
which  they  throw  into  large  holes  dug  in  the  ground,  where 
the  whole  mass  is  soon  turned  into  a  "  stinking  jelly."  The 
Russian  Government,  disapproving  of  the  Kamtschadales' 
favorite  food,  which  is  certainly  disgusting  to  any  European 
and  must  be  unwholesome,  endeavored  to  introduce  the  salt- 
ing of  fish  by  stringent  regulations.  Arrangements  were  made 
at  Petropaulowski  for  obtaining  salt  from  sea-water,  and  the 
salt  was  sold  to  the  Kamtschadales  at  a  nominal  price.  The 
Kamtschadales,  who  are  an  uncommonly  docile  race,  obeyed 
orders,  and  the  fish  was  conscientiously  salted.  But  they  did 
not  eat  it.  They  kept  to  their  decomposing  fish ;  and  at  the 
time  that  Ditmar  was  in  Kamschatka,  the  Russian  Govern- 
ment had  relinquished  the  task  of  persuading  them  as  hopeless. 
Only  the  old  people  still  spoke  of  that  period  as  of  a  time  of 
plague.  Ditmar  relates  that  the  descendants  of  the  Russians 
in  Kamschatka  do  cultivate  European  vegetables,  but  only  in 
small  quantities,  that  they  prefer  the  Kamtschadales'  bill  of 
fare,  and  accordingly  their  use  of  salt  has  gradually  diminished. 
Vegetables  and  cereals  are  only  eaten  in  any  quantity  in  Petro- 
paulowski, and  here,  on  the  other  hand,  the  salt-cellar  is  always 
on  the  table. 

The  astronomer,  L.  Schwarz,  informed  me  that  on  his 
travels  in  the  country  of  the  Tunguses,  he  lived  exclusively  on 
reindeer-flesh  and  game.  This  diet  agreed  perfectly  with  him, 
and  he  never  experienced  any  wish  for  salt. 

But  as  it  might  be  thought  that  the  disinclination  of  the 
Siberian  tribes  for  salt  might  be  due,  not  to  the  animal  food, 
but  to  the  northern  climate,  I  will  refer  to  the  accounts  of  the 
inhabitants  of  warm  countries  who  live  on  an  animal  diet,  and 
yet  take  no  salt. 

In  the  Neilgherry  Hills  in  India,  a  pastoral  tribe,  the  Tudas, 
was  first  discovered  during  the  present  century.  Owing  to 
their  being  surrounded  by  fever  marshes,  the  English  had  al- 
ways been  prevented  reaching  them.  They  were  totally  unac- 
quainted with  vegetable  food,  and  lived  on  milk  and  bufiFalo- 
meat,  knowing  nothing  of  salt. 

The  Kirghese  also  live  on  meat  and  milk,  and  never  use 
salt,  although  they  are  inhabitants  of  the  salt  steppes.     I  was 


THE    lis  ORGANIC    FOOD-STUFFS  95 

informed  of  .this  by  Baron  Maydell,  who  travelled  through  the 
Kirghese  Steppes  in  1845  and  in  1847. 

Sallust  relates  the  same  thing  of  the  Numidians  :  "  Numidse 
plerumque  lacte  et  ferina  carne  vescebantur  et  neque  salem 
neque  alia  irritamenta  gulae  quserebant."  There  is  an  abun- 
dance of  salt  on  the  north  coast  of  Africa. 

At  present  there  are  certain  tribes  of  Bedouins  in  Arabia 
who  live  under  conditions  similar  to  those  of  the  Numidians  in 
the  time  of  Sallust.  In  Wrede's  Travels  it  is  stated  that  the 
Bedouins  eat  meat  without  salt,  and  appear  to  consider  the  use 
of  salt  as  altogether  ridiculous. 

The  Bushmen  in  the  south  of  Africa  live  by  the  chase,  and 
do  not  use  any  salt. 

The  negro  races  on  the  contrary  are  agriculturists.  The 
interior  of  Africa  contains  but  little  salt.  At  the  present  time 
the  negroes  are  plentifully  supplied  with  salt,  both  by  importa- 
tion and  by  salt-boiling  on  the  coast.  Among  the  older  trav- 
ellers, Mungo  Park  gives  the  following  description  of  the 
longing  of  the  negroes  for  salt :  "  In  the  districts  of  the  in- 
terior, salt  is  the  greatest  of  all  delicacies.  It  strikes  a  Euro- 
pean very  strangely  to  observe  a  child  sucking  a  piece  of  rock- 
salt  as  if  it  were  sugar.  I  have  frequently  seen  this  done, 
although  the  poorer  class  of  inhabitants  in  the  interior  are  so 
badly  provided  with  this  costly  article,  that  to  say  that  a  man  eats 
salt  with  his  meal  is  equivalent  to  saying  that  he  is  rich.  I  my- 
self have  found  the  scarcity  of  this  natural  product  very  trying. 
Constant  vegetable  food  causes  a  painful  longing  for  salt  that 
is  quite  indescribable.  On  the  coast  of  Sierra  Leone  the  desire 
for  salt  was  so  keen  among  the  negroes  that  they  gave  away 
wives,  children,  and  everything  that  was  dear  to  them,  in  return 
for  it." 

The  Indians  of  North  America  are  well  known  to  have  been 
hunters  and  fishermen  at  the  time  of  their  discovery  ;  they  did 
not  use  salt,  although  the  North  American  prairies  are  full  of  it. 
Only  a  few  tribes  on  the  lower  course  of  the  Mississippi  were 
diligent  tillers  of  the  soil  at  the  time  of  the  first  invasion  of  the 
Spaniards.  It  is  related  of  these  tribes  that  they  waged  wars 
about  the  salt-springs. 

The  Mexicans  were  farmers,  and  understood  the  methods  of 
obtaining  salt.  The  same  account  is  given  of  the  natives  whom 
Columbus  met  with  in  the  West  Indian  Islands. 

The  shepherds  of  the  South  American  pampas,  who  live 
entirely  on  meat  and  regard  vegetable  food  as  fit  only  for 
animals,  do  not  use  any  salt,  although  the  pampas  abound  in 
numberless    salt-lakes    and    incrustations.      The    neighboring 


96  .  LECTURE  vn 

Araucanians,  on  the  other  hand,  who  were  farmers  at  the  time 
of  the  discovery  of  America,  made  use  both  of  sea-salt  and  rock- 
salt.  The  inhabitants  of  New  Holland  were  hunters,  and  em- 
ployed no  salt. 

Most  of  the  tribes  of  Australia  and  of  the  East  Indian 
Archipelago  live  on  a  mixed  diet,  and  get  enough  salt  from  the 
marine  animals  that  they  eat.  But  there  is  an  account  of  one 
purely  agricultural  tribe  in  the  tropical  islands,  where  the 
people  live  almost  exclusively  on  the  produce  of  the  field,  which 
is  rich  in  potassium.  They  are  the  Battas  in  Sumatra.  We 
should  expect  that  these  people  would  have  a  great  desire  for 
salt.  For  a  long  time  I  was  unable  to  find  any  account  about 
it  in  any  books  of  travel,  till  at  last  I  lighted  upon  a  passage  in 
a  chapter  describing  then"  modes  of  legal  procedure,  in  which  it 
said  that  the  solemn  form  of  oath  in  use  among  them  ran  as  fol- 
lows :  "  May  my  harvest  fail,  my  cattle  die,  and  may  I  never 
taste  salt  again,  if  I  do  not  speak  the  truth." 

From  the  above  facts  we  see  that  at  every  period,  in 
every  part  of  the  world,  and  in  every  climate,  there  are 
people  who  use  salt  as  well  as  those  who  do  not.  The 
people  who  take  salt,  though  differing  from  each  other  in 
every  other  respect,  are  all  characterized  by  a  vegetable  diet ; 
in  the  same  way,  those  who  do  not  use  any  salt  are  all  alike 
in  taking  animal  food.  We  see  that  whole  tribes,  when 
forsaking  their  nomadic  life  for  an  agricultural  one,  begin  the 
use  of  salt ;  and  that,  vice  versa,  people  who  have  been 
accustomed  to  take  salt,  cease  to  do  so  when  they  emigrate 
and  settle  down  among  a  flesh-eating  population.  We  see 
that  European  travellers,  if  their  supply  of  salt  fails  them  in 
foreign  countries,  do  not  feel  any  want  of  it  if  they  are  living 
on  animal  food ;  but  that,  on  the  other  hand,  they  experience 
"  a  painful  longing  "  for  it  if  they  adopt  a  vegetarian  mode  of 
diet.  The  causal  connection  between  vegetable  food  and  the 
need  for  salt  is  undeniable.  It  might  be  still  doubted  whether 
it  is  really  the  abundance  of  potassium  in  the  vegetables  which 
causes  this  need.  The  occurrence  of  potassium  in  considerable 
quantity  is  not  the  only  difference  between  vegetable  and  ani- 
mal food.  The  following  facts  may  serve  to  confirm  my  view 
of  the  matter  : — 

One  important  article  of  vegetable  diet,  rice,  is  very  poor  in 
potassium  salts.  Rice  contains  six  times  less  potassium  than 
the  European  cereals  (wheat,  rye,  barley),  from  ten  to  twenty 
times  less  than  the  leguminosse,  and  from  twenty  to  thirty 
times  less  than  the  potato.  If  we  consume  enough  rice  to 
yield  100  grms.  of  proteid,  we  only  take  in  1  grm.  K2O  from 


THE    INORGANIC    FOOD-STUFFS 


97 


the  same  source.  But  if  we  consume  100  grms.  of  proteid  in 
the  form  of  potatoes,  we  should  at  the  same  time  obtain  above 
40  grms.  K^O.  We  should  therefore  expect  people  who  only 
take  rice  and  no  other  vegetable  with  their  meat  to  have  no 
desire  for  salt.  This  is  in  fact  the  case,  and  is  universally  re- 
corded of  certain  tribes  of  Bedouins  on  the  Arabian  Peninsula, 
and  of  a  few  races  in  the  East  Indian  Islands. 

L.  Lapicque  has  objected  to  my  hypothesis  on  the  grounds 
that  certain  negro  races,  who  can  obtain  no  common  salt,  use 
instead  as  an  adjunct  to  their  vegetable  food  the  ashes  of  a 
plant  consisting  chiefly  of  potassium  salts.  I  cannot  regard  my 
hypothesis  as  controverted  by  this  fact,  unless  it  were  shown 
that  these  negroes  had  a  choice  between  common  salt  and  salts 
of  potash  and  gave  the  preference  to  the  latter.  If  however 
they  are  driven  by  need  to  the  potash  salts,  it  is  possible  that 
we  have  here  merely  an  example  of  disordered  instinct,  for 
which  we  have  other  analogies.  A  man  who  has  always  taken 
alcohol  instead  of  water  to  quench  his  thirst  prefers  the  former 
to  the  latter,  although  the  alcohol  has  the  effect  of  increasing 
rather  than  of  diminishing  his  thirst. 

The  amount  of  potassium  and  sodium  in  the  different  articles 
of  vegetable  and  animal  food  eaten  by  man  and  animals  may  be 
gathered  from  the  following  tables  : 


TABLE  I. 
In  1000  Pakts  of  Dried  Stjbstakces  the  Proportions  are — 


Arranged  according  to  increasing  amount 
of  potassium. 


Arranged  according  to  increasing 
amountj,of  sodium. 


Kice  . 

Bullock's  blood  . 
Oats       ) 
Wheat  I 

Eye  •    •    •    • 

Barley  i 

Dog's  milk  .    .    . 
Human  milk  .    . 

Apples 

Peas  .    .        .    . 
Milk  of  herbivora 

Hay 

Beef 

Beans    

Strawberries    .    . 

Clover  

Potatoes   .... 


K,0. 


1 

2 

5-6 

5-6 
5-6 
11 
12 

9-17 
6-18 
19 
21 
22 
23 
20-28 


Na,0. 


0.03 
19.0 

0.1-  0.4 

2.0-  3.0 
1.0-  2.0 

0.1 

0.2 
1.0-10.0 
0.3-  1.5 

3.0 

0.1 

0.2 

0.1 
0.3-  0.6 


Rice 

Apples    .    .    .    .    . 

Beans  

Peas 

Clover     

Oats      "I 
Wheat  I 

Barley  (  •  •  ■  • 
Eye       J 

Potatoes 

Hay  .  .  .  .  . 
Human  milk  .  .  . 
Dog's  milk  .  .  , 
Milk  of  herbivora 

Beef 

Bullock's  blood     . 


Na,0. 


0.03 
0.07 
0.13 
0.17 
0.17 

0.1-  0.4 

0.3- 
0.3-  1.5 
1.0-  2.0 
2.0-  3.0 
1.0-10.0 
3.0 

19.0 


98 


LECTTJEE    VII 


We  see  from  the  second  table  that  the  beast  of  prey,  which 
devours  every  part  of  an  animal,  obtains  potassium  and  so- 
dium in  almost  equal  quantity.  This  is  the  case,  not  only  with 
mammals,  but  with  the  whole  class  of  vertebrates.^  On  the 
other  hand,  four  equivalents  of  potassium  are  present  for  every 
equivalent  of  sodium  in  the  bloodless  meat  of  slaughtered  ani- 
mals. It  is  therefore  noteworthy  that  the  people  who  live  on 
an  animal  diet  without  salt,  carefully  avoid  loss  of  blood  when 
they  slaughter  the  animals.  This  was  told  me  by  four  dif- 
ferent naturalists,  who  have  lived  among  flesh-eaters  in  various 
parts  of  northern  Russia  and  Siberia.  The  Samoyedes,  when 
dining  off  reindeer-flesh,  dip  every  mouthful  in  blood  be- 
fore eating  it.  The  Esquimaux,  in  Greenland,  are  said  to 
plug  the  wound  as  soon  as  they  have  killed  a  seal.^  Among 
the  Masai,  a  tribe  of  eastern  equatorial  Africa,  who  during 
their  period  as  warriors  from  seventeen  to  twenty-four  years 
of  age,  live  exclusively  on  an  animal  diet  without  salt,  blood  is 
regarded  as  the  choicest  and  most  desirable  of  all  articles  of 
food.^ 

TABLE  II. 
Foe  One  EquivAiiENT  NAjO  the  Equivalents  of  KjO  are 


Bullock's  blood 
Egg-albumin  .   .    . 
Yolk  of  egg    .    .    . 
The  wbole  body  of  mam 

mals  .  .    . 

Milk  of  Carnivora  . 
Mangel-wurzel    .    . 
Human  milk 
Milk  of  herbivora  . 

Beef 

Wheat 


Equivalent 
K,0 


0.07 

0.7 
1.0 

0.7-  1.3 
0.8-  1.6 

2.0 
1.0-  4.0 
0.8-  6.0 

4.0 
12.0-23.0 


Barley    .    . 

Oats     .    .    . 

Rice    .    .    . 

Eye 

Hay 

Potatoes 

Peas 

Strawberries 

Clover 

Apples    .    . 

Beans .    .    . 


Equivalent 
K,0 


14-21 

15-21 

24 

9-57 

3-57 

31-42 

44-50 

71 

90 

100 

110 


The  two  bases  are  also  contained  in  the  milk  of  Carnivora 
in  equal  proportions,  whereas  potassium  generally  preponde- 
rates largely  in  the  milk  of  herbivora  and  in  human  milk,  as 


1  A.  von  Bezold,  "Das  chemische  Skelett  der  Wirbelthiere,"  Zcitschr.  für 
wissenschaftl.  Zoologie,  vol.  ix.  p.  241 :  1858  ;  G.  Bunge,  Zeitschr.  f.  Biolog.,  vol. 
X.  p.  .318 :  1874. 

2  The  exact  source  of  these  facts  is  given  in  the  Zeitschr.  f.  Biolog.,  vol.  x.  p. 
11.5  (note) :  1874. 

3  Vide  H.  H.  Johnston,  "  Kilimandjaro." 


THE    INOEGANIC    FOOD-STUFFS  99 

may  be  seen  by  a  reference  to  Table  II.  This  shows  that  man 
and  herbivora  can  do  very  well  on  a  diet,  in  which  the  relation 
is  from  four  to  six  equivalents  of  potassium  to  one  equivalent 
of  sodium,  without  any  addition  of  salt.  And  there  are  many 
vegetables  in  which  the  proportion  is  no  higher.  In  hay, 
which  is  a  mixture  of  all  kinds  of  herbage,  the  proportion  is 
sometimes,  as  the  above  table  shows,  only  as  three  to  one.  It 
is  a  fact  that  many  wild  herbivorous  mammals,  such  as  hares 
and  rabbits,  never  eat  salt,  and  in  many  places  it  is  not  offered 
to  herbivorous  domestic  mammals.  A  keen  desire  for  salt  would 
only  be  awakened  in  these  animals  if  they  were  exclusively  fed 
on  one  of  the  varieties  of  herbage  containing  both  the  most 
potassium  and  the  least  sodium,  such  as  clover.  The  wild 
herbivora  perhaps  instinctively  avoid  browsing  only  on  the 
herbage  that  contains  the  largest  proportion  of  potassium. 
But  the  domesticated  animals  would  suffer  if  they  were  given 
food  that  was  very  rich  in  potassium,  without  salt.  I  will  not 
affirm  that  they  could  not  exist  under  this  treatment,  although 
farmers  have  found  by  experience  that  the  animals  eat  more 
and  thrive  better  if  they  are  allowed  to  have  salt,  and  even 
that  obvious  ill-effects  follow  a  complete  abstinence  from  this 
article.^  Nor  do  I  maintain  that  human  beings  cannot  exist 
without  salt  on  a  diet  almost  entirely  vegetarian.  But  if  we 
had  no  salt,  we  should  have  a  strong  disinclination  to  eat  large 
quantities  of  a  vegetable  rich  in  potassium,  such  as  potatoes. 
The  use  of  salt  enables  us  to  employ  a  larger  variety  of  the 
earth's  products  as  food  than  we  could  without  it. 

It  is  particularly  worthy  of  note  that  those  articles  of  diet 
in  which,  according  to  Table  II.,  the  proportion  of  potassium 
to  sodium  is  the  highest,  such  as  rye,  potatoes,  peas,  and  beans, 
are  the  very  ones  that  form  the  staple  food  of  the  lower  classes 
in  Europe.  The  injustice  of  a  salt-tax  is  therefore  apparent, 
for  the  poorer  a  man  is  the  more  he  is  forced  to  live  on  the 
vegetables  containing  the  largest  amount  of  potassium,  and  the 
greater  his  consumption  of  salt  in  consequence. 

In  passing,  I  must  call  attention  to  the  fact  that  we  are 
accustomed  to  take  far  too  much  salt  with  our  viands.  Salt  is 
not  only  an  aliment,  it  is  also  a  condiment,  and  easily  lends 
itself,  as  all  such  things  do,  to  abuse.  A  glance  at  Table  III. 
shows  us  how  little  salt  need  be  added  to  most  articles  of  diet 

1  Barral,  "  Statique  chimique  des  animaux,  appliquee  speeialement  ä  la 
question  de  I'emploi  agricole  du  sei "  :  Paris,  1850 ;  Boussingault,  Ann.  de  Chim. 
et  de  Phys.,  ser.  Ill,  vol.  xxii.  p.  116:  1848.  Demesmay,  Journal  des  J^cono- 
mistes,  vol.  xxv.  pp.  7,  251:  1849;  Desaive,  "  Ueber  den  vielseitigen  Nutzen 
des  Salzes  in  der  Landwirthschaft,"  Deutsch  von  Protz :  Leipzig,  1852. 


100 


LECTUEE    VII 


in  order  to  preserve  the  same  proportion  of  the  alkalies  as  ia 
milk.  For  instance,  from  1  to  2  grms.  of  salt  in  the  day 
would  be  sufficient  to  add  to  a  diet  of  cereals  and  legumiaosse, 
or  a  few  decigrammes  to  a  diet  of  rice.  Instead  of  this,  most 
people  take  from  20  to  30  grms.  daily,  and  frequently  even 
more. 

TABLE  III. 

Fob  evilry  One  Hundred  Gems,  op  Proteid  we  get — 


• 

K.O. 

Na„0. 

Bullock's  blood 

Eice 

Beef.   ...            

Wheat  ) 

Eye       [ 

0.2  grms. 
1.0      " 
2.0      " 

2.0-5.0      " 

5.0-6.0      " 
42      " 

2.0    grms. 
0.03      " 
0.3 

0.05-0.3        " 

Peas     J 

Human  milk 

1.0  -2.4        " 

Potatoes           

0.7        " 

We  must  ask  whether  our  kidneys  are  really  able  to 
eleminate  such  large  quantities  of  salt  ?  Do  we  not  impose  too 
great  a  task  upon  them,  and  may  it  not  be  fraught  with 
serious  consequences  ?  When  on  a  diet  of  meat  and  bread, 
without  salt,  we  excrete  not  more  than  from  6  to  8  grms.  of 
alkaline  salts  in  twenty-four  hours.  With  a  diet  of  potatoes, 
and  a  corresponding  addition  of  salt,  over  100  grms.  of 
alkaline  salts  pass  through  the  kidneys  in  the  day.  May  not 
there  be  danger  in  this  ?  The  habit  of  drinking  spirituous 
liquors,  which  moreover  is  reckoned  one  of  the  causes  of 
chronic  nephritis,  also  brings  about  the  immoderate  use  of 
salt,^  and  thus  one  sin  against  nature  leads  to  another.  These 
are  questions  to  which  I  would  direct  the  attention  of  practi- 
tioners. 

There  is  no  organ  in  our  body  so  mercilessly  ill  treated  as 
the  kidneys.  The  stomach  reacts  against  overloading.  The 
kidneys  are  obliged  to  let  everything  pass  through  them,  and 
the  harm  done  to  them  is  not  felt  till  it  is  too  late  to  avoid  the 
evil  consequences. 

I  would  further  call  attention  to  the  slight  amount  of 
work  that  devolves  upon  the  kidneys  when  rice  is  the  staple 
food.     Only  2  grms.  of  alkaline  salts  are  excreted  in  twenty- 

1  Compare  H.  Keller  (Bunge's  laboratory),  ^ez^scAr.  f.physiol.  Chem.,  vol. 
xiii.  pp.  130  and  134 :  1889. 


THE   INOBGANIC   FOOD-STUFFS  101 

four  hours.  .  The  superiority  of  rice  (which  has  for  centuries 
been  the  food  of  the  majority  of  mankind — Persians,  Indians, 
Chinese,  Japanese)  over  potato  is  evident.  Should  not  rice 
be  employed  as  a  chief  article  of  diet  in  patients  with  renal 
disease?  The  same  with  affections  of  the  stomach,  for  the 
potassium  salts  act  as  a  powerful  irritant  to  the  gastric  mucous 
membrane,'  and  rice  contains  less  of  these  than  any  other  article 
of  food. 

I  cannot  leave  this  subject  without,  in  conclusion,  giving 
expression  to  one  other  theory  which  is  becoming  more  and 
more  a  conviction  with  me,  and  in  proof  of  which  I  have  car- 
ried out  a  series  of  troublesome  experiments.  I  have  not 
hitherto  ventured  to  publish  them,  because  I  was  well  aware 
that  the  theory  might  be  thought  very  fanciful  while  the 
grounds  upon  which  it  was  built  were  still  so  scanty.  I  am 
however  convinced  that  the  remarkably  high  percentage  of 
salt  in  vertebrate  animals,  as  well  as  the  desire  to  take  salt 
with  our  food,  can  only  be  satisfactorily  explained  by  the  theory 
of  evolution. 

Let  us  glance  at  the  distribution  of  the  two  alkalies,  po- 
tassium and  sodium,  over  the  whole  surface  of  the  globe.  In 
our  introductory  remarks  on  the  circulation  of  the  elements,  I 
mentioned  the  struggle  that  went  on  between  the  carbonic  acid 
and  the  silicic  acid  for  the  possession  of  the  bases  (see  p.  15). 
In  this  conflict  the  carbonic  acid  shows  a  greater  affinity  for 
sodium,  and  the  silicic  acid  for  potassium.  By  the  action  of 
the  weather  on  silicic  rocks,  the  sodium,  after  decomposition, 
is  dissolved  in  water  as  a  carbonate,  and  trickles  with  the 
water  into  the  ground.  The  potassium  on  the  contrary,  with 
other  bases,  especially  alumina,  remains  combined  with  the 
silicic  acid,  and  continues  to  lie  on  the  surface  as  an  insoluble 
double  salt.  When  the  sodium  carbonate  reaches  the  sea  by 
means  of  springs,  streams,  and  rivers,  it  is  converted  by  the 
chlorids  of  the  alkaline  earths  into  common  salt,  the  insoluble 
carbonates  of  the  alkaline  earths  are  formed,  which  sink  to 
the  bottom,  and  are  continually  building  up  whole  mountain 
ranges  in  the  shape  of  lime,  chalk,  and  dolomite.  Sea- water  is 
thus  rich  in  common  salt,  poor  in  potassium  salts,  while  the 
surface  of  dry  land  is  rich  in  potassium  salts  and  poor  in 
common  salt. 

The  amount  of  common  salt  in  the  organism  corresponds 
with  the  amount  in  the  environment.  Sodium  differs  in  this 
respect  from  potassium,  which    is   an   integral,  indispensable 

^G.  Bunge,  Zeitschr.f.  Biolog.,  vol.  ix.  p.  130:  1873;  and  Pfliiger's  Arch., 
vol.  iv.  pp.  277,  280:  1871. 


102  LECTURE   VII 

constituent  of  every  vegetable  and  animal  cell.  Every  cell 
has  the  power  of  withdrawing  and  of  assimilating  the  requisite 
amount  of  this  base,  even  from  the  most  scantily  supplied  soil. 
All  sea  and  land  plants  therefore  contain  an  abundance  of 
potassium.  Sodium  on  the  other  hand  does  not  appear  to  play 
such  an  important  part.  Many  plants  contain  only  traces  of 
sodium ;  those  which  are  rich  in  it  are  only  the  sea-weeds  and 
the  plants  which  grow  on  the  sea-shore,  and  on  the  salt  steppes 
which  are  dried-up  sea-basins.  There  are  only  a  few  apparent 
exceptions  to  this  rule,  as  for  instance  in  the  classes  of  Cheno- 
podium  and  Atriplex.  But  these  species  thrive  only  in  a 
saline  soil ;  they  are  closely  allied  to  the  denizens  of  the  salt 
steppes,  and  have  probably  migrated  from  there.  Among  cul- 
tivated plants,  the  Beta  altissima,  which  also  belongs  to  the 
Chenopodiacese,  is  the  only  one  rich  in  sodium,  and  this  was 
originally  indigenous  on  the  sea-coast. 

This  is  also  the  case  with  invertebrate  animals ;  only  those 
which  live  in  the  sea,  and  those  nearest  allied  to  them  on  land, 
contain  much  salt.  The  typical  representatives  of  land  inverte- 
brates, the  insects,  have  very  little  salt  in  them.  I  have  myself 
made  an  analysis  which  proves  that  they  do  not  contain  more 
sodium  than  the  plants  from  which  they  derive  their  nourish- 
ment. 

The  land  vertebrates  are  all  remarkably  rich  in  salt,  in  spite 
of  the  scanty  supply  around  them.  But  even  these  are  only 
apparent  exceptions.  We  need  but  remember  the  fact  that  the 
first  vertebrates  on  our  planet  all  lived  in  the  sea.  Is  not  the 
large  amount  of  chlorid  of  sodium  found  in  the  present  inhabi- 
tants of  dry  land  another  proof  of  the  genealogical  connection 
which  we  are  forced  to  accept  from  morphological  facts  ?  There 
is  no  doubt  that  each  of  us  in  his  individual  development  has 
gone  through  a  stage  in  which  he  still  possessed  the  chorda 
dorsalis  and  the  branchial  arches  of  his  sea-dwelling  ancestors. 
Why  may  not  the  high  average  of  salt  in  our  tissues  be  also  in- 
herited from  them  ? 

If  this  interpretation  be  correct,  we  should  expect  that  the 
younger  the  vertebrates  are  in  their  individual  development, 
the  more  salt  they  would  possess.  This  is  in  fact  the  case.  I 
have  convinced  myself  by  numerous  experiments  that  an 
embryo  of  a  mammal  contains  more  salt  than  a  new-bom 
animal,  and  that  it  gradually  becomes,  after  birth,  poorer  in 
chlorin  and  sodium  as  it  develops.  Cartilage  contains  the 
most  sodium  of  any  tissue  in  our  bodies,  besides  being  also  the 
tissue  of  greatest  antiquity.  It  is  histologically  identical 
with  the  tissue  which  still    survives    in    the  skeleton    of  the 


THE   INOEGAJSriC    FOOD-STUFFS  103 

Selachians,  -a  salt-water  animal,  during  its  whole  life.  The 
human  skeleton,  as  every  one  knows,  is  originally  also  composed 
of  cartilage,  and  even  before  birth  much  of  this  is  replaced  by 
bone.  This  phenomenon  cannot  be  understood  on  teleological 
grounds;  it  can  only  be  explained  by  the  theory  of  evolution. 
We  cannot  assume  that  the  cartilage  period  must  be  passed 
through  in  order  that  the  bone  may  develop  from  the  cartilage. 
This  is  not  the  fact.  Bone  does  not  arise  from  cartilage. 
The  cartilage  is  entirely  absorbed,  and  the  bone  grows  from 
the  perichondrium  to  take  the  place  of  the  cartilage.  And 
moreover  the  oldest  formation,  the  cartilage,  also  contains  the 
largest  proportion  of  sodium. 

These  are  facts  which  lead  most  readily  to  the  interpreta- 
tion that  the  vertebrates  living  on  dry  land  originally  came 
from  the  sea,  and  are  still  continuing  to  adapt  themselves  to 
their  present  surroundings,  where  they  can  get  but  little  salt. 
We  prolong  this  process  of  acclimatization  by  taking  advantage 
of  the  salt  strata  which  have  been  left  on  the  land  by  our 
primeval  element,  the  salt  flood. 


LECTURE  VIII 

MILK   AND   THE   FOOD   OF   INFANTS 

We  have  already  had  occasion  in  considering  food-stuffs  to 
make  frequent  mention  of  milk,  the  nourishment  which  nature 
provides  for  the  growing  organism,  and  we  may  now  consider 
this  subject  more  in  detail. 

In  the  following  table  I  give  the  results  of  the  analyses  of 
milk/  so  far  as  they  have  been  carried  out  up  to  the  present 
time : — 

One  Hundred  Parts  of  Mix,k  Contain — 


HumaQ. 

Dog. 

Cat 

Rabbit 

Guinea- 

Sow 

Elephant. 

I. 

II. 

III. 

pig- 

Casein 

_ 

1.2 

_ 

5.2 

3.1 

_ 

_ 

_ 

_ 

Albumin  . 

— 

0.5 

— 

1.9 

6.4 

— 

— 

— 

— 

Total  Proteids .    .    . 

1.7 

1.7 

1.5 

7.1 

9.5 

15.5 

11.2 

5.9 

3.1 

Fat                        .    . 

3.1 

3.8 

3.3 

12.5 

3.3 

10.5 

45.8 

6.9 

19.6 

Sugar  of  milk 

5.9 

6.0 

6.5 

3.5 

4.9 

2.0 

1.3 

3.8 

8.8 

Ash           

0.2 

0.2 

0.3 

1.3 

0.6 

2.6 

0.6 

1.1 

0.7 

'  In  the  cases  of  mare's,  cow's,  goat's,  and  sheep's  milk,  I  have  taken  the 
average  figures  as  calculated  by  J.  König  in  his  "Chemistry  of  Human  Food- 
stuffs," 3d  edition,  Berlin,  1889.  The  few  older  and  less  reliable  analyses  have 
been  superseded  by  the  numerous  later  ones  carried  out  according  to  accurate 
methods.  For  sow's  milk  I  have,  in  calculating  the  average  composition,  adopted 
only  the  last  four  of  König's  nine  analyses  since  the  earlier  analyses,  in  con- 
sequence of  the  incomplete  extraction  of  the  casein  precipitate  with  ether, 
obviously  give  too  small  an  amount  of  fat  and  too  large  a  one  of  casein.  For  the 
same  reason  I  have  only  employed  for  dog's  milk  two  analyses  of  my  pupil  Fr. 
Pröscher,  in  which  the  fat  was  completely  extracted  by  means  of  the  Soxhlet 
apparatus  {Zeitschr.  f.  physiol.  Chem.,  vol.  xxiv.  p.  290:  1897).  The  analysis 
of  rabbit's  milk  is  by  A.  Pizzi  {Le  staz.  sperim.  agric.  ital.,  vol.  xxvi.  p.  615 : 
1894) ;  that  of  reindeer  milk  by  Fr.  Werenskiold  {Chemikerzeitung,  vol.  xix., 
1895)  ;  that  of  porpoise  milk  by  Frankland  {The  Chemical  News,  vol.  Ixi.  p. 
63:  1890).  The  mean  figures  for  the  milk  of  the  remaining  animals  are 
reckoned  from  the  small  number  of  analyses  which  have  so  far  been  made  and 
are  to  be  found  in  König's  work.  Finally,  as  regards  human  milk,  nearly  all 
the  analyses  have  been  carried  out  by  inaccurate  methods.  After  close  in- 
vestigation, it  seems  to  me  that  the  analyses  of  the  following  authors  are  the 
most  worthy  of  confidence :  (1)  Emil  Pfeiffer,  Jahrb.  f.  Kinderheilkunde,  vol.  xx. 
p.  389:  1883;  (2)  .lulius  Lehmann,  Pflüger's  Arch.,  vol.  Ivi.  p.  577:  1894;  (3) 
Söldner,  Zeitschr.  f.  Biolog.,  vol.  xxxiii.  p.  66  :  1896.  The  average  compositions 
obtained  by  these  three  authors  are  given  separately  in  the  following  tables  as 

104 


MILK   AND   THE   FOOD    OF   INFANTS 


105 


One  Hundred  Pakts  of  Milk  Contain  (continued)- 


Horse. 

Don- 
key. 

Cow. 

Goat. 

Sheep. 

Rein- 
deer. 

Camel. 

Llama. 

Porpoise. 

( Glohiocephalus 

melas.) 

Casein     .... 

1.2 

0.7 

3.0 

3.2 

5.0 

8.4 



3.0 



Albumin    .    .    . 

0.8 

1.6 

0.5 

1.1 

1.6 

2.0 

— 

0.9 

— 

Total  Proteids  . 

2.0 

2.2 

3.5 

4.3 

6.5 

10.4 

4.0 

3.9 

7.61 

Fat. 

1.2 

1.6 

3.7 

4.8 

6.9 

17.1 

3.1 

3.2 

43.8 

Sugar  of  milk  . 

5.7 

6.0 

4.9 

4.5 

4.9 

2.8 

5.6 

5.6 

— 

Ash 

0.4 

0.5 

0.7 

0.8 

0.9 

1.5 

0.8 

0.8 

0.5 

ANALYSES  OF  ASH. 
One  Thousand  Parts  of  Milk  Contain- 


Man. 

Dog. 

Horse. 

Cow. 

Goat. 

Sheep. 

KjO 

0.780 

1.41 

1.05 

1.77 

2.35 

1.17 

Na^O 

0.232 

0.81 

0.14 

1.11 

0.52 

1.08 

CaO 

0.328 

4.53 

1.24 

1.60 

2.10 

2.72 

MgO      ....... 

0.064 

0.20 

0.13 

0.21 

0.36 

0.50 

FejOs 

0.004 

0.02 

0.02 

0.004 

0.015 

0.04 

P2O5 

0.473 

4.93 

1.31 

1.97 

3.22 

4.12 

CI 

0.438 

1.63 

0.31 

1.70 

2.04 

1.34 

The  composition  of  the  milk  in  various  mammals  is  thus  very- 
striking  in  its  variability.  So  far  as  I  know,  no  attempt  has 
been  made  to  explain  this  diflPerence.  It  appears  to  me  that  a 
teleological  explanation  may  be  found  in  the  diiferent  rate  of 
growth  of  the  sucklings.  It  is  a  plausible  conjecture  that  a 
more  rapidly  growing  animal  needs  a  milk  richer  in  those  con- 
stituents which  serve  particularly  to  build  up  tissue — proteid 
and  inorganic  salts.  This  connection  appeared  in  the  analyses 
of  milk  ^  which  I  published  in  1874. 


One  Hundred  Parts  of  Milk  Contained — 


Proteid. 

Ash. 

Human 

1.4 

1.8 
4.0 
9.9 

0.22 

Horse .... 

0.41 

Cow 

0.80 

Doff 

1.31 

Nos.  I.,  II.,  and  III.  It  speaks  well  for  these  figures  that,  although  obtained  by 
very  different  methods,  they  all  agree  well  with  each  other.  The  analyses  of 
the  ash  are  obtained  from  G.  Bunge,  Zeitschr.  f.  Biolog.,  vol.  x.  p.  295:  1874; 
and  from  Fr.  Pröscher,  loc.  cit. 

^  Proteids  and  sugar  of  milk. 

2  G.  Bunge,  Zeitschr.  f.  Biolog.,  vol.  x.  p.  295:  1874. 


106 


LECTUEE   VIII 


Now  it  is  well  known  that  the  infant  grows  more  slowly  than 
the  foal,  the  foal  than  the  calf,  the  calf  than  the  dog.  In  order 
to  see  whether  this  theory  held  good  universally  I  suggested 
to  Mr.  Pröscher  that  he  should  estimate  the  rapidity  of  growth 
of  the  domestic  animals  during  lactation,  as  so  far  the  weights 
at  different  periods  had  only  been  ascertained  in  the  case  of 
infants,  foals,  and  calves.^  In  the  following  table  I  give  the 
results  of  these  weighings  as  well  as  the  most  reliable  average 
figures  of  the  proteid  and  ash  of  the  milk.  Of  the  constituents 
of  the  ash,  the  amounts  of  phosphoric  acid  and  lime  are  par- 
ticularly mentioned,  since  these  substances  are  especially  con- 
cerned in  the  building  up  of  the  tissues.  The  alkaline  chlorids 
stand  in  a  different  position,  and  play  an  important  part  in 
excretion.^ 

One  Hundred  Parts  of  Milk  Contain — 


Time  in  which  the  body-weight 

of  the  uew-born  animal 

was  doubled. 

Proteid. 

Ash. 

Lime. 

Phosphoric 
acid. 

Man           180  days 

Horse  .    .    60     " 

Cow.    .    .    47     " 

Goat    .    .    19     " 

Pig.            18     " 

Sheep          10     " 

Dog.   .    .      8     "     

Cat  .    .    .      7     " 

1.6 
2.0 
3.5 
4.3 
5.9 
6.5 
7.1 
9.5 

0.2 
0.4 
0.7 
0.8 

0.9 
1.3 

0.328 
1.24 
1.60 
2.10 

2.72 
4.53 

0.473 
1.31 
1.97 
3.22 

4.12 
4.93 

These  results  thus  confirm  in  a  striking  manner  the  sug- 
gestion which  was  put  forward  above.  The  agreement  would 
perhaps  be  still  more  complete  if  the  specimens  of  milk 
analyzed  had  all  been  taken  at  the  time  that  the  weight 
was  first  doubled.  A  sample  of  the  milk  should  be  analyzed 
every  day  from  the  date  of  birth  until  that  on  which  the 
weight  was  doubled,  and  the  average  of  these  analyses  taken. 
For  instance,  the  amount  of  proteid  and  ash  in  the  milk 
diminishes  with  the  duration  of  lactation.  The  suckling  grows 
the  most  rapidly  directly  after  birth,  and  increases  in  weight 
by  degrees  more  and  more  slowly.  The  composition  of  the 
milk  varies  in  accordance  with  the  growth.  The  same  law 
which  we  have  laid  down  in  the  case  of  the  various  mammals 
also  holds  good  for  the  various  stages  of  development  in  the 
individual.     My  attention  was  directed  to  their  connection  by 


iFr.  Pröscher,  Zeitschr.  f.  Biolog.,  vol.  xxiv.  p.  285:  1897. 
2  Compare  the  agreement  in  the  composition  of  the  ash  of  milk  and  that  of 
the  suckling  discussed  in  the  last  chapter. 


MILK    AND    THE    FOOD    OF    INFANTS  107 

an  analysis -of  milk  published  in  1874.  Thus  in  one  woman 
during  the  first  month  after  birth  the  milk  contained  1 5  per 
mille  proteid,  whereas  in  the  tenth  month  the  amount  had 
dropped  to  9  per  mille ;  the  proportion  of  ash  having  likewise 
decreased.^  The  diminution  of  proteid  in  the  milk  as  lactation 
proceeds  has  also  been  observed  and  tabulated  by  other  authors 
for  man  and  animals.^ 

It  has  long  been  known  that  the  proportion  of  proteid  in 
milk  is  very  large  from  the  first  to  the  third  day  after  birth, 
and  this  may  be  recognized  without  any  quantitative  estimation 
from  the  fact  that  this  milk,  to  which  the  name  of  colostrum 
has  been  given,  coagulates  on  boiling.  As  a  practical  result  of 
this  fact,  a  wet  nurse  can  never  completely  replace  the  mother 
unless  her  infant  has  been  born  on  the  same  day  as  her  foster 
child. 

As  regards  the  remarkable  difference  in  the  amounts  of  fat 
and  sugar  in  the  milk  of  various  animals,  we  might  anticipate 
that  here  climate  might  have  the  same  influence  that  we  have 
seen  it  to  possess  for  the  food  of  man  in  cold  and  hot  coun- 
tries. As  already  mentioned,  people  in  cold  regions  instinc- 
tively adopt  a  diet  rich  in  fat  and  poor  in  sugar,  while  the 
converse  is  the  case  among  the  inhabitants  of  warm  countries. 
Correspondingly  we  find  the  milk  of  animals  which  originally 
lived  in  a  warm  climate,  rich  in  sugar  and  poor  in  fat  (camel, 
llama,  horse,  donkeyj,  while  the  milk  of  animals  inhabiting 
the  North  is  rich  in  fat  and  poor  in  sugar  (reindeer).  The 
composition  of  human  milk  shows  that  the  human  race  was 
cradled  in  the  warmer  regions  of  the  earth  and  supports  a 
hypothesis  which  is  based  on  many  other  grounds.  The  ex- 
ception to  this  rule,  e.  g.,  the  higher  percentage  of  fat  in  the 
milk  of  the  elephant,  a  native  of  southern  climes,  may  be  more 
apparent  than  real.  It  is  possible  that  the  elephant  may  be  de- 
scended from  a  northern  ancestor,  since  the  mammoth  is  known 
to  have  lived  during  the  diluvial  period  in  the  present  home  of 
the  reindeer.  The  elephant  may  therefore  have  emigrated 
southwards  and  have  partially  preserved  the  original  compo- 
sition of  the  milk.  A  thorough  comparative  analysis  of  the 
milk  of  all  mammals  may  perhaps  be  the  means  in  the  future 
of  controlling  all  the  conclusions  which  have  been  arrived  at 
by  comparative  anatomists,  paleontologists,  systematists,  and 
natural  historians. 

The   high   percentage  of  fat   in   the   milk  of  the  dolphin 

1  G.  Bunge,  loc.  cit.,  pp.  316  and  317. 
_  ^Th.  Brunner,  Pfliiger's  Arch.,  vol.  vii.  p.  440:  1873;  Siedamgrotzky  u.  Hof- 
meister, Mitth.  a.  d.  chtm.  physiol.  Versuchsst.  d.  Thierarzneischule  in  Dresden, 
1879.    H.  Weiske  u.  G.  Kennepohl,  Journ  f.  Landw.,  vol.  xxix.  p.  451 :  1881. 


108  LECTURE    VIII 

(^Globiocephalus  melas)  (three  times  as  much  as  in  that  of  the 
reindeer)  may  be  explained  on  two  grounds,  firstly,  that  it  lives 
in  high  latitudes,  and  secondly,  that,  being  an  aquatic  animal,  it 
is  surrounded  by  a  better  conductor  of  heat  than  is  the  case  with 
animals  that  live  on  land,  and  so  needs  for  the  maintenance  of 
its  temperature  a  higher  proportion  of  the  food-stuff  with  the 
greatest  potential  energy,  i.  e.,  fat. 

The  great  amount  of  fat  in  the  milk  of  guinea-pigs  cannot 
be  explained  in  this  way,  since  these  animals  come  originally 
from  a  tropical  country — Peru.  From  the  first  day  of  birth  the 
guinea-pig  picks  up  its  own  food  by  the  mother's  side.  The  milk 
in  this  case  plays  but  a  secondary  part  therefore  in  its  nutrition, 
and  only  supplies  a  welcome  addition  to  the  vegetable  food  so 
deficient  in  fat. 

These  observations  show  how  carefully  nature  has  provided 
for  the  supply  of  all  necessary  food-stuffs  in  their  due  propor- 
tions. It  is  therefore  not  a  matter  of  indifference  whether  the 
young  derives  its  nourishment  from  its  own  mother  or  from  the 
milk  of  another  animal,  or  even  from  an  artificial  food.  Even 
were  the  constituents  and  their  proportions  in  the  milk  known 
to  us,  the  preparation  of  such  an  artificial  food  would  present 
considerable  difficulties.  But  we  must  acknowledge  that  we  are 
possibly  not  even  acquainted  with  all  the  constituents.  For  in- 
stance, the  various  proteids  and  nucleins  of  milk  have  not  yet 
been  separated  out  as  chemical  entities,  nor  have  their  charac- 
teristics in  this  condition  been  studied.  And  finally  there  is  the 
possibility  that  milk  may  contain  small  amounts  of  substances 
not  yet  discovered,  which  may  nevertheless  play  an  important 
part  in  nutrition. 

Now  in  consequence  of  the  degeneration  of  our  race  and  as 
a  result  of  the  indifference  of  many  mothers,  the  necessity  for 
the  artificial  rearing  of  infants  frequently  arises. 

A  glance  at  the  table  on  p.  106  shows  that  if  cow's  milk  be 
diluted  with  an  equal  volume  of  water  the  amount  of  proteid 
is  nearly  the  same  as  in  human  milk.  The  total  ash  is  only 
slightly  higher ;  the  quantity  of  lime  however  is  two  and  a  half 
times,  that  of  phosphoric  acid  twice  as  great.  The  smaller 
proportion  of  sugar  and  fat  can  be  supplied  by  the  addition  of 
sugar  of  milk  and  cream. 

Instead  of  a  solution  of  sugar  of  milk,  cow's  milk  is  some- 
times diluted  with  solutions  of  other  forms  of  sugar  as  well 
as  with  starchy  decoctions  from  all  kinds  of  cereals.^     Which 

^  An  account  of  the  comprehensive  literature  on  the  subject  of  the  artificial 
feeding  of  infants  is  given  by  Ph.  Biedert,  "  Die  Kinderernährung  im  Säuglings- 
alter," 3d  edit.,  Stuttgart,  1897,  and  by  E,  Feer,  Jahrb.  f.  Kinderheilk.,  N.  F., 
vol.  xlii.  p.  195  :  1896. 


MILK  AND  THE  FOOD  OF  INFANTS  109 

of  these  is  the  more  digestible  for  infants  it  is  difficult  to  decide 
owing  to  individual  variations ;  hence  for  the  present  no  rule 
can  be  laid  down,  especially  as  no  trustworthy  statistics  are 
available  on  this  subject. 

Experience  however  shows  that  many  children  are  incapable 
of  digesting  any  form  of  diluted  cow's  milk,  and  that  in  no 
case  does  it  completely  replace  the  mother's  milk. 

What  are  the  reasons  for  this  fact  ? 

1.  The  caseinogen  of  human  milk  is  not  identical  with  that 
of  cow's  milk,  as  is  shown  by  the  varying  proportion  of  phos- 
phorus and  sulphur.  The  caseinogen  belongs  to  the  so-called 
nucleo-albumins,  i.  e.,  to  the  substances  which  on  artificial  di- 
gestion split  up  into  peptone  and  a  substance  resembling  nu- 
clein.  The  caseinogens  therefore  invariably  contain  considerable 
amounts  of  phosphoric  acid  as  well  as  some  lime.  According 
to  Lehmann  and  Hempel  ^  the  percentage  of  phosphate  of  lime 
in  the  caseinogen  of  human  milk  is  3.2,  and  in  cow's  milk  6.6. 
The  proportion  of  sulphur  in  the  two  cases  is  1.1  per  cent.,  and 
0.72  per  cent. 

A  complete  and  accurate  analysis  of  cow's  caseinogen  has 
been  made  by  Hammarsten.^  This  may  be  compared  wäth  the 
analysis  of  the  caseinogen  of  human  milk,  which  was  carried 
out  by  Wroblewski  ^  under  Drechsel's  guidance. 


Caseinogen. 

From  cow's  milk. 

From  human  milk. 

C     52.96 

52.24 

H      7.05 

7.32 

N    15.65 

14.97 

S       0.74 

1.11 

P       0.84 

0.68 

0     22.78 

23.66 

2.  By  the  action  of  rennet  ferment  "*  in  the  stomach,  the 

1  Jul.  Lehmann  u.  W.  Hempel,  Pflüger's  Arch.,  vol.  Ivi.  p.  574:  1894. 

2  Hammarsten,  Zeitschr.  f.  physiol.  Chem.,  vol.  vii.  p.  269:  1883;  and 
vol.  ix.  p.  296 :  1885. 

^A.  Wroblewski,  "Beitr.  zur  Kenntniss  des  Frauenmilcheaseins  u.  seiner 
Unterschiede  vom  Kuhcasein."     Dissert.,  Bern,  1894. 

*  The  significance  of  rennet  ferment  and  of  casein  coagulation  in  the  stomach 
is  still  unexplained.  For  a  knowledge  of  the  experiments  which  have  been  made 
with  a  view  to  the  elucidation  of  this  problem  I  recommend :  Hammarsten, 
Upsala  läkareförennings  Förhandlingar,  8,  p.  63  :  1872 ;  9,  pp.  363  and  452  : 
1874  (complete  account  in  Maly's  Jahresber.  f.  Thier  Chemie).  "  Zur  Kenntniss 
des  Caseins  u.  der  Wirkung  des  Labferments,"  Upsala,  1877.  Hoppe-Seyler' s 
Zeitschr.,  vol.  xxii.  p.  103:  1896.  Alex.  Schmidt,  "Beitr.  z.  Kenntniss  der 
Milch,"  Dorpat,  1874.  M.  C.  du  Saar,  "  Melkstremmende  werking  van  den 
maaginhoad  bij  jonge  zuigelingen.,"  Diss.,  Amsterdam,  1890.  M.  Arthus  et  C. 
Pages,  Arch,  de  Physiol.,  1890,  pp.  331  and  540.    3{em.  soc.  Mol.,  vol.  xliii. 


110  LECTURE   VIII 

caseinogen  of  human  milk  coagulates  in  fine  floccula,  that  of 
cow's  milk  in  coarse  lumps,  which  by  many  children  cannot  be 
digested.  If  the  cow's  milk  be  diluted  with  a  solution  of 
milk-sugar,  the  coarse  precipitation  is  prevented.  Although 
by  such  means  it  is  possible  to  avoid  the  aggregation  of  the 
precipitate  into  solid  lumps,  this  clot  still  remains  closer, 
tougher,  and  more  indigestible  than  that  of  human  milk.  This 
seems  to  depend  on  the  greater  percentage  of  lime  and  the 
smaller  alkalinity  of  cow's  milk.  As  Soxhlet^  has  clearly 
pointed  out,  any  attempt  to  get  rid  of  these  differences  is  beset 
with  great  difficulties,  which  at  present  are  in  practice  almost 
insuperable. 

It  might  have  been  anticipated  that  better  results  would  be 
obtained  if  instead  of  cow's  milk  the  milk  of  some  animal  which 
in  its  composition  more  closely  resembled  human  milk  were  em- 
ployed. A  glance  at  the  Table  on  p.  105  shows  that  this  is 
especially  the  case  with  mares'  and  asses'  milk.  But  so  far  we 
have  too  slight  a  practical  experience  to  argue  upon. 

3.  To  add  to  the  other  difficulties  of  artificial  feeding  there 
remains  the  necessity  for  sterilization.  Milk  is  a  most  fertile 
nutrient  medium  for  all  kinds  of  microorganisms,  which  in- 
crease in  it  at  an  incredible  rate.  Fresh  milk,  which  contained 
9000*  bacteria  in  one  c.cm.  when  first  brought  into  the  labora- 
tory, showed  an  hour  later  31,750  ;  after  nine  hours,  120,000  ; 
and  after  twenty-four  hours,  5,600,000.^ 

A  short  exposure  to  the  boiling  temperature  does  not  suffice 
to  destroy  all  bacteria.  If  still  higher  temperatures  be  em- 
ployed, the  sugar  is  attacked  and  causes  the  milk  to  become 
brown.  For  the  best  method  of  approximately  sterilizing  milk 
without  greatly  impairing  its  nutritive  value,  the  reader  may  be 
referred  to  the  latest  accounts  in  the  works  of  P.  Cazeneuve,^  L. 
Fürst,"*  A.  Baginsky,^  and  a  summary  of  the  literature  by 
Biedert,  loo.  cit. 

p.  131 :  1891.  Zdzislaw  Szydlowski,  Prager  med.  Wochenschr.,  No.  32 :  1892. 
Pages,  Comptes  rendus,  vol.  cxviii.  p.  1291  :  1894.  E..  Peters,  "  Das  Lab  u.  die 
Labähnlichen  Fermente."  Gekrönte  Preisschrift,  Rostock,  1894.  M.  Arthus, 
Arch,  de  Physiol.,  vol.  xxvi.  p.  257 :  1895.  A.  Edmunds,  Journ.  of  Physiol., 
vol.  xix.,  Nos.  5  and  6:  1896.  F.  S.  Locke,  The  Journ.  of  Experimental  Med., 
vol.  ii..  No.  5  :  1897. 

1  F.  Soxhlet,  "  Die  ehem.  Unterschiede  zwischen  Kuh  u.  Frauenmilch  u.  die 
Mittel  zu  ihrer  Ausgleichung."  Vortrag  gehalten  am  11.  Jan.  1893.  Münch. 
med.  Wochenschr.,  1893.  Compare  O.  Heubner,  Berliner  Hin.  Wochenschr., 
vol.  xxxvii.  pp.  841  and  870 :  1894. 

2  Miquel,  Journ.  de  Pharm,  et  de  Chim.,  vol.  xxi.  p.  565 :  1890.  Compare 
E.  V.  Freudenreich,  Milchzeitung,  p.  33 :  1890. 

^  P.  Cazeneuve,  Bull,  de  la  Soc.  chim.  de  Paris,  vol.  xiii.  p.  502 :  1895. 
•*  L.  Fürst,  Deutsche  Medicinalzeitung,  p.  1007  :  1895. 
*A.  Baginsky,  Berliner  klin.  Wochenschr.,  No.  18:  1895. 


MILK    AND    THE    FOOD    OF    INFANTS  111 

4.  Finally  with  anything  but  the  mother's  milk  there  is  the 
constant  danger  of  over-feeding  the  infant.  When  taking  the 
breast,  the  fatigue  consequent  upon  the  effort  of  sucking  ap- 
pears to  prevent  the  infant  taking  more  than  the  proper  amount, 
whereas  from  the  feeding  bottle,  which  can  be  drawn  without 
effort,  the  infant  takes  more  than  it  can  digest,  with  consequent 
dyspepsia.^ 

From  these  remarks  it  will  readily  be  seen  that  artificial 
feeding  is  fraught  with  grave  danger. 

If  on  the  one  hand  we  observe  how  carefully  nature  has 
adapted  the  composition  of  milk  to  the  needs  of  every  species 
of  mammal,  and  if  on  the  other  we  consider  how  ignorant  we 
are  concerning  the  nature  of  the  food-stuffs,  the  digestive  proc- 
esses in  the  infant  and  the  disturbances  which  these  are  liable 
to  from  the  myriad  microorganisms  in  the  intestines,  it  is  not 
a  matter  for  wonder  that  in  spite  of  the  greatest  efforts  the 
natural  diet  for  infants  has  not  so  far  been  successfully  replaced 
by  any  artificial  food.  In  support  of  this  contention  we  may 
quote  the  following  statistics  : — 

In  1890  49,362  children  were  born  alive  in  Berlin.  Before 
the  end  of  their  first  year  12,623  of  these  children  had  died. 
Of  these — 

1588  had  been  fed  at  the  breast ; 
8008  had  been  fed  with  cow's  milk. 

The  remaining  infants  had  been  brought  up  on'milk  and  arti- 
ficial foods,  or  upon  these  latter  alone.  No  deduction  however 
can  be  drawn  from  the  influence  of  the  food  on  the  mortality 
unless  we  know  what  proportion  of  the  whole  number  of  chil- 
dren born  were  reared  at  the  breast.  The  following  figures 
enable  us  to  form  an  approximate  idea.  The  census  taken  De- 
cember 1,  1890,  showed  that  there  were  then  in  Berlin  39,312 
children  under  the  age  of  one  year.     Of  these — 

20,812  were  breast-fed  ; 
16,620  were  reared  by  hand. 

Therefore  of  the  breast-fed  children  one  in  thirteen  died ; 
whereas  of  those  brought  up  by  hand  the  mortality  rose  to  one 
out  of  every  two  infants. 

No  doubt  this  excessively  high  rate  of  infant  mortality  is 
due  not  only  to  the  unnatural  mode  of  diet,  but  partly  to  the 
neglect  which  is  doubtless  in  many  cases  associated  therewith ; 
since  a  mother  who  nurses  her  child  would  also,  as  a  general 
rule,  instinctively  lavish  more  care  upon  it. 

1 E.  Feer,  loc.  cit,,  p.  196. 


112  LECTUEE    VIII 

The  mortality  among  children  reared  on  artificial  foods  is 
much  higher  even  than  among  those  fed  on  cow's  milk.^ 

Heathen  races  have  frequently  sanctioned  infanticide.  Chris- 
tian races  torture  their  children  slowly  to  death.  Artificial  feed- 
ing was  unknown  to  the  ancients.^ 

When  children  are  breast-fed,  the  condition  of  the  mother's 
health  acts  both  on  the  quantity  and  the  quality  of  the  milk 
secreted.^  But  the  quality  of  the  milk  seems  to  be  but  little 
dependent  upon  the  nature  of  the  diet.  Occasionally  an  in- 
crease of  fat  is  observed  after  very  abundant  feeding ;  but 
the  amount  of  the  other  constituents  in  the  milk  is  hardly 
altered. 

Taking  milk  as  our  starting  point,  let  us  now  proceed  to 
consider  the  diet  normally  required  by  the  adult.  In  the  case 
of  the  infant  we  are  acquainted  with  the  natural  composition  of 
the  food ;  we  can  also  ascertain  the  exact  quantity  provided  by 
nature  by  weighing  the  infant  before  being  placed  at  the  breast 
and  again  after  it  has  instinctively  satisfied  its  hunger.  The 
difference  in  weight  gives  the  amount  of  milk  taken,  and  the 
repetition  of  this  process  at  each  meal  gives  the  total  amount 
for  the  twenty-four  hours. 

The  most  recent  and  exact  estimates  of  this  kind  have  been 
carried  out  by  E.  Feer.*  He  determined  the  amount  taken  by 
a  boy  from  birth  until  the  30th  week,  and  found  that  in  the 
last  week  he  took  951  grms.  of  milk  daily.  At  this  time  the 
child's  weight  was  8226  grms.  From  the  average  composition 
of  human  milk,  viz. : — 

Proteid 1.6  per  cent. 

Fat 3.4        " 

Sugar 6.1        " 

Ash 0.2        " 

we  can  compute  the  absolute  amount  of  the  nutriment  daily 
taken  in — 

Proteid 15.2 

Fat 32.3 

Sugar 58.0 

Ash 1.9 

Statistisches  Jahrbuch  der  Stadt  Berlin.  Doppeljahrgang  xvi.,  xvii. 
Statistik  der  Jahre  1889  und  1890,  pp.  30  and  148 :  Berlin,  1893. 

2  Biedert,  loc,  dt.,  p.  155. 

^  An  account  of  the  very  comprehensive  literature  on  this  subject  is  given  by 
Biedert,  loc.  cit.,  chap.  iii. 

*  The  latest  experiments  concerning  the  influence  of  the  food  on  the  compo- 
sition of  human  milk  are  those  of  P.  Baum  ("Die  Frauenmilch,"  Sammlung 
klinischer  Vorträge  von  Volkmann,  No.  105,  p.  202,  et  seq.,  Leipzig,  1894).  The 
earlier  literature  is  here  quoted.  Experiments  on  animals  have  given  essentially 
the  same  results.  For  the  extensive  literature  on  this  subject  the  text-books  on 
agriculture  should  be  consulted. 


MILK    AND    THE    FOOD    OF    INFANTS  113 

According  to  the  same  proportions  a  man  of  70  kilos,  would 
take  in — 

Proteid 129 

Fat        275 

Sugar 494 

Ash 16 

These  figures  agree  very  well  with  the  observations  which  have 
been  made  directly  on  the  adult.  I  have  already  mentioned 
that  a  man  in  full  work,  who  can  procure  sufficient  food  for 
himself,  eats  daily — 

Proteid 100-150 

Fat 50-200 

Carbohydrates 300-800 

It  might  be  thought  that  the  amount  of  proteid  for  the 
adult  reckoned  from  that  required  by  the  infant  would  be  a 
maximum  value,  since  the  young  animal  needs  larger  quantities 
of  proteid  for  the  growth  of  its  tissues,  whereas  the  man  has 
only  to  maintain  his  existing  store.  But  it  must  be  remem- 
bered that  the  sexual  functions  of  the  adult  are  likewise  a  form 
of  growth — "  growth  beyond  the  boundaries  of  the  individual." 
This  growth  of  the  tissues  in  man  consists  in  the  production  of 
spermatozoa,  in  woman  in  the  development  of  the  embryo  or 
the  formation  of  menstrual  fluid.  The  growth  beyond  the 
boundary  of  the  individual  appears  in  women  during  the  child- 
bearing  period  to  be  only  in  abeyance  during  the  time  of 
lactation,  when  the  milk  with  its  rich  complement  of  proteid 
is  secreted.  But  the  secretion  of  milk  may  be  regarded  as  a 
growth  of  tissue,  since  as  a  matter  of  fact  the  fat-laden  epithelial 
cells  of  the  mammary  glands  either  partially  or  completely 
break  up  and  are  regenerated.^ 

But  the  amount  of  fat  (275  grms.)  calculated  for  the  adult 
from  that  required  by  the  infant  is  certainly  too  high.  The 
infant  has  relatively  a  much  larger  body-surface  and  therefore 
gives  ofi*  more  heat ;  it  thus  requires  larger  quantities  of  the  food- 
stuif  that  produces  the  greatest  heat  in  its  combustion. 

The  figure  494  for  the  carbohydrates  agrees  very  well  with 
the  mean  numbers  obtained  in  direct  experiments  on  adults. 
A  young  man  eighteen  years  of  age  who  took  nothing   but 

^  The  latest  researches  on  the  histological  processes  involved  in  the  secretion 
of  milk  are  those  of  F.  Nissen,  Arch.  f.  mikr.  Anat.,  vol.  xxvi.  p.  337:  1886. 
E.  Coen,  Beitr.  2.  pathol.  Anat.  u.  Physiol,  v.  Ziegler  u.  Nauwerck,  vol.  ii.  p. 
83:  1887.  P.  R.  Kadkin,  Diss.  Petersburg :  1890  (in  Russian).  Frommel,  ^rcA. 
/.  Gynäk.,  vol.  xl.,  Hft.  ii.:  1891 ;  and  Centralbl.  f.  Gynäkol.,  p.  471 :  1891.  J. 
Steinhaus,  Du  Bois'  Arch.,  Physiol.  Abth.  Supplementband,  p.  54:  1892. 


114  LECTURE    VIII 

cow's  milk  (compare  the  conclusion  of  Lecture  XXV.)  drank 
three  liters  a  day,  containing — 

Proteid 105 

Fat Ill 

Sugar 147 

Ash 21 

His  state  of  nutrition  was  certainly  bad  and  his  powers  of 
work  poor.  But  it  cannot  be  decided  whether  this  should  be 
referred  to  an  insufficient  income  of  some  organic  food-stuff  or 
merely  to  the  absence  of  iron.     (See  Lecture  XXV.) 


LECTURE    IX 


SUBSIDIAEY    ARTICLES    OF   DIET 


Man,  together  with  all  animals,  consumes  certain  articles 
which  are  neither  sources  of  energy  nor  possessed  of  reparative 
power  for  the  continual  body  waste.  They  are  eaten  on  account 
of  the  agreeable  influence  which  they  exert  on  the  nerves  of 
taste  or  smell  or  on  other  parts  of  the  nervous  system.  We  call 
these  substances  condiments  and  stimulants.  They  are  as  nec- 
essary to  us  as  the  food-stuffs  themselves. 

It  is  a  very  noticeable  fact  that  our  most  important 
organic  food-stuffs  are  absolutely  without  taste  or  odor.  We 
can  only  smell  volatile  matter,  or  taste  such  substances  as  are 
soluble  in  water.  Our  organic  food-stuffs  have  neither  of  these 
properties.  They  are  not  in  the  least  volatile,  and  are  almost 
all  insoluble  in  water.  Fats,  as  we  well  know,  are  not  miscible 
with  water,  and  proteids  only  swell  without  actually  dissolving 
in  it.  Of  the  carbohydrates,  the  sugars  alone  are  soluble,  and 
they  taste  sweet.  In  the  case,  then,  in  which  food  is  possessed 
of  any  taste  at  all,  it  is  agreeable.  Since  the  bulk  of  our  food 
can  produce  no  effect  on  our  organs  of  sense,  we  find  our  organs 
of  taste  and  smell  so  adapted  that  the  volatile  and  soluble 
matters,  which  are  constantly  associated  with  aliments  as  they 
occur  in  nature,  produce  agreeable  sensations  when  they  act  on 
these  sense-organs.  These  sensations  not  only  increase  our 
desire  for  food ;  they  also  help  digestion.  It  is  a  matter  of 
common  experience,  that  even  the  imagination  of  fragrant  and 
savory  food  may  augment  the  secretion  of  saliva.  The  in- 
creased secretion  of  gastric  juice  produced  by  the  same  cause 
has  been  observed  on  dogs  with  a  gastric  fistula.  To  show 
them  from  a  long  distance  a  piece  of  meat  is  sufficient  to 
excite  the  secretion  of  the  gastric  juice.  Thus,  if  a  gastric 
fistula  be  established  in  a  dog,  and  at  the  same  time  the 
esophagus  be  divided,  so  that  all  food  taken  in  by  the  mouth 
falls  out  by  the  opening  in  the  esophagus  without  reaching 
the  stomach,  it  is  observed  that  every  act  of  taking  food  by 
the  mouth  causes  a  large  secretion  of  gastric  juice  containing 
both  hydrochloric  acid   and   pepsin,  although   the   food  does 

115 


116  LECTURE   IX 

not  reach  the  stomach.  This  reflex  secretion  is  abolished  by 
division  of  both  vagi.^  It  is  hence  probable  that  the  ac- 
tivity of  all  other  glands  associated  with  digestion  is  reflexly 
aroused  by  agreeable  tastes  and  smells,  and  that  all  processes 
and  movements  which  are  involved  in  digestion  and  absorption 
are  hereby  assisted.  Pleasant  sensory  impressions  produce  a 
cheerful  frame  of  mind,  and  thus  indirectly  tend  to  act  favor- 
ably on  all  the  processes  of  the  body.  On  the  other  hand  it  is 
a  familiar  fact  that  disagreeable  smells  and  tastes  cause  a  dis- 
turbance of  digestion  which  may  even  induce  vomiting.  The 
necessity  of  these  adjuncts  to  food  is  then  beyond  doubt ; 
every  effort  to  consume  food  which  has  neither  taste  nor  smell 
would  soon  fail. 

Whilst  animals  merely  take  such  sapid  substances  as  occur 
naturally  mixed  with  the  food  they  eat,  man  goes  much  further 
by  artificially  separating  the  subsidiary  from  the  necessary 
aliments.  He  takes  the  former  by  themselves,  or  with  only  a 
small  proportion  of  the  latter.  Hence  arises  for  man  the 
danger  of  excess.  The  regulating  mechanism,  which  in  animals 
consists  of  the  feeling  of  satiety  which  sets  in  as  soon  as  they 
have  eaten  enough,  tends  to  be  disturbed.  So  long  as  only  the 
senses  of  taste  and  smell  are  concerned,  there  is  but  little 
danger  of  excess.  The  more  intense  the  stimulation  of  the 
organs  of  smell  and  taste,  the  more  rapidly  is  the  sensibility  of 
our  nerves  blunted ;  we  get  tired  of  the  impressions  made  upon 
them.  But  besides  those  substances  which  act  agreeably  on 
our  senses,  man  has  learnt  to  isolate  others  which  produce 
pleasurable  sensations  by  their  action  on  the  functions  of  the 
brain  ;  these  we  term  narcotics.  He  has  discovered  them  even 
when  they  cannot  be  detected  by  smell  or  taste,  and  when  they 
occur  only  in  plants  which  have  no  nutritive  value  ;  such  are 
opium,  tea,  coffee,  hashish,  &c.  Others,  which  nature  does  not 
produce,  he  has  learnt  to  prepare  artificially  from  innocuous 
substances,  as  for  instance  alcohol  from  sugar.  Conscious 
volition  disturbs  the  harmonious  action  of  the  unconscious  in- 
stincts, and  becomes  the  source  of  unlimited  misery. 

So  long  as  we  are  unacquainted  with  the  chemical  processes 
by  which  these  subsidiary  articles  of  diet  act  on  the  nervous 
system,  their  special  consideration  is  a  subject  rather  for  toxi- 
cology and  the  physiology  of  the  nervous  system  than  for 
physiological  chemistry.  I  shall  therefore  treat  of  only  a  few 
which  are  still  often  considered  to  be  true  aliments.  The  most 
important  of  these  are  alcoholic  drinks. 

1  J.  P.  Pawlow  and  E.  0.  Schumowa  Simanowskaja,  Du  Bois'  Arch.,  p.  53, 
1895. 


SUBSIDIARY    ARTICLES    OF    DIET  117 

We  kno.w  that  alcohol  is  to  a  very  great  extent  oxidized 
in  the  body.  Only  a  small  part  is  excreted  unchanged  by  the 
kidneys  and  lungs.^  Alcohol  is  therefore  without  doubt  a 
source  of  energy  when  absorbed  into  the  body.  But  it  does 
not  therefore  follow  that  it  is  a  food.  To  prove  this'  it  would 
be  necessary  to  show  that  the  energy  liberated  by  the  oxidation 
of  alcohol  is  used  to  aid  the  performance  of  a  normal  function. 
It  is  not  enough  that  chemical  potential  energy  is  transformed 
into  kinetic  energy ;  the  transformation  must  occur  at  the 
right  time,  in  the  right  place  and  in  definite  parts  of  the 
tissues.  The  tissues  are  not  so  constituted  that  they  can  be 
fed  with  any  and  every  combustible  material ;  we  do  not  know, 
for  instance,  whether  alcohol  can  serve  as  a  source  of  the 
energy  by  virtue  of  which  the  functions  of  muscle  and  nerve 
are  performed  (see  Lecture  XXIII.). 

It  will  be  objected  that  the  heat  which  is  produced  by  the 
combustion  of  alcohol  must  in  any  case  be  useful  to  our 
organism.  Even  if  it  does  not  directly  subserve  any  definite 
function  of  a  particular  organ,  the  combustion  of  the  alcohol 
must  economize  the  consumption  of  other  food-stuffs.  But 
even  this  cannot  be  admitted.  For  whilst  on  the  one  hand 
the  alcohol  increases  the  production,  on  the  other  it  increases 
the  loss,  of  heat.  Owing  to  the  paralyzing  action  which  it 
exerts  on  the  vasomotor  system,  a  dilatation  of  the  vessels, 
and  especially  of  the  cutaneous  vessels,  occurs,  and  consequently 
there  is  an  increased  loss  of  heat.  The  total  result  is  a 
diminution  of  the  temperature  of  the  body,  which  has  been 
actually  proved  to  take  place. 

Alcohol  has  invariably  a  paralyzing  influence.  All  the  re- 
sults which,  on  superficial  observation,  appear  to  show  that 
alcohol  possesses  stimulant  properties,  can  be  explained  on  the 
ground  that  they  are  due  to  paralysis.^ 

'  Vict.  Subbotin,  Zeitschr.  f.  Biolog.,  vol.  vii.  p.  361 :  1871 ;  Dupre,  Proc. 
Roy.  Soc,  vol.  XX.  p.  268 :  1872 ;  and  I'he  Practitioner,  vol.  ix.  p.  28 :  1872 ; 
Anstie,  Practitioner,  vol.lxiii.  p.  15 :  1874 ;  Aug.  Schmidt,  Centralbl.  f.  d.  med, 
Wissen^ch.,  No.  23, 1875 ;  H.  Heubach,  "  Ueber  die  Ausscheidung  des  Weingeistes 
durch  den  Harn  Fiebernder,"  Dissert.:  Bonn,  1875 ;  C.  Binz,  Ärch.  f.  exper.  Path, 
u.  Pharm.,  vol.  vi.:  1877 ;  H.  Heubach,  "  Quantitative  Bestimmung  des  Alkohols 
im  Harn,"  Arch.  f.  exp.  Path.  u.  Pharm.,  vol.  viii.  p.  446  :  1878 ;  G.  Bodländer, 
Pflüger's  Arch.,  vol.  xxxii.  p.  398  :  1883. 

2  With  regard  to  this  matter,  we  recommend  the  perusal  of  the  short  and 
lucid  description  in  Schmiedeberg's  "Grundriss  der  Arzneimittellehre,"  2d 
edit.,  pp.  25,  27:  Leipzig,  Vogel,  1883.  Compare  Zimmerberg,  Dissert.,  Dorpat, 
1869.  Maki,  Dissert.,  Strassburg,  1884.  H.  Dreser,  "Arch.  f.  exper.  Path.  u. 
Pharm.,"  vol.  xxvii.  p.  87  :  1890.  P.  v.  d.  Mühll  and  A.  Jaquet,  Correspondenz- » 
hlatt  f.  schweizer  Aerzte,  No.  15,  p.  457,  1891,  and  E.  Krsepelin,  "  Ueb.  d. 
Beeinflussung  einfacher  psychischer  Vorgänge  durch  einige  Arzneimittel.  Jena, 
Fischer,  1892 ;  A.  Smith,  Bericht  üb.  d.  V.  internat.  Congress  z.  Bekämpfung  des 


118  LECTURE    IX 

It  is  a  common  idea  that  alcohol  produces  a  warming  ef- 
fect in  cold  weather.  This  feeling  of  warmth  depends,  in  the 
first  place,  on  the  fact  already  noticed — that  the  paralysis  of 
the  central  nervous  system  causes  an  increased  blood-supply  to 
the  surface  of  the  body ;  and  secondly,  in  all  probability,  on  the 
blunting  of  the  sensibility  of  the  central  organs  which  are  con- 
cerned in  the  sensation  of  cold. 

The  stimulating  action  which  alcohol  appears  to  exert  on  the 
psychical  functions  is  also  only  a  paralytic  action.  The  cere- 
bral functions  which  are  first  interfered  with  are  the  powers  of 
clear  judgment  and  criticism.  As  a  consequence,  emotional 
life  comes  into  free  play  unhampered  by  the  guiding-strings 
of  reason.  The  individual  becomes  confiding  and  communi- 
cative ;  he  forgets  his  cares  and  becomes  gay ;  in  fact,  he  no 
longer  clearly  sees  the  dangers  and  difficulties  of  life.  But  the 
most  pronounced  paralyzing  action  of  alcohol  is  seen  in  the 
way  it  allays  all  sorts  of  discomfort  and  pain,  and,  above  all, 
the  worst  sort  of  pain — mental  suffering,  anxiety,  and  trouble. 
Hence  the  light-heartedness  which  prevails  at  a  carouse.  It  is 
a  prejudice  which  depends  upon  self-deception,  to  believe  that 
a  man  ever  becomes  witty  by  aid  of  spirituous  drinks.  This 
error  is  simply  one  of  the  results  of  the  paralytic  influence 
mentioned  above ;  as  the  power  of  criticising  one's  self 
diminishes,  self-complacency  increases.  The  lively  gesticula- 
tions and  useless  exertions  of  intoxicated  people  are  due  to 
paralysis,  the  inhibitory  influence,  which  prevents  a  sober  man 
from  uselessly  expending  his  strength,  being  removed.  Asso- 
ciated with  this  is  the  increased  frequency  of  pulse,  which  is 
commonly  cited  as  an  instance  of  the  stimulating  power  of 
alcohol ;  it  has  nothing  to  do  with  the  action  of  alcohol,  but  is 
caused  by  the  surroundings  among  which  the  alcoholic  drinks 
are  generally  taken.  It  is  a  consequence  of  the  excited  condi- 
tion, and,  according  to  the  experiments  hitherto  made,  does  not 
occur  when  the  body  remains  quiet.^ 

A  paralytic  symptom,  which  is  erroneously  regarded  as  one 
of  stimulation,  is  also  found  in  the  deadening  of  the  sense 
of  fatigue.  There  is  a  strong  belief  that  alcohol  gives  new 
strength  and  energy  after  fatigue  has  set  in.     The  sensation  of 

Missbrauches  geistiger  Getränke,  Basel,  p.  341 :  1896  ;  C.  Fürer,  ibid.,  p.  355 ;  G. 
Aschaifenburg,  "Psychologische  Arbeiten  v.  E.  Krsepelin,"  vol.  i.  p.  608:  1896. 
C.  Binz  ("Der  Weingeist  als  Heilmittel,"  Sonderabdruck  aus  den  Verhandlungen 
des  VII.  Congresses  f.  innere  Medicin  zu  Wiesbaden,  1888 :  Wiesbaden,  Verlag 
von  J.  F.  Bergmann,  1888)  upholds  the  older  view,  according  to  which  alcohol 
•has  a  stimulating  action  when  taken  in  small  doses. 

1  Schmiedeberg,  loc.  cit.,  p.  26;  Zimmerberg,  "  Unt.  üb.  den  Einfluss  des 
Alkohols  auf  die  Thätigkeit  des  Herzens,"  Dissert.,  Dorpat,  1869.  P.  v.  d. 
Mühll  and  A.  Jaquet,  Gorrespondenzblatt  f.  schweizer  Aerzte,  p.  457 :  1891. 


SUBSIDIARY    ARTICLES    OF    DIET  119 

fatigue  is  one  of  the  safety-valves  of  our  machine.  To  stifle 
the  feeling  o'f  fatigue  in  order  to  be  able  to  work  on,  is  like 
forcibly  closing  the  safely-valve  so  that  the  boiler  may  be  over- 
heated. 

That  this  prejudice  concerning  the  '  strengthening '  power  of 
alcohol  maintains  so  firm  a  hold  is  to  be  explained  by  the  ex- 
periences of  habitual  drinkers.  Any  one  who  is  in  the  regular 
habit  of  taking  a  considerable  quantity  of  alcohol  is  better  able 
to  do  his  work  while  he  continues  it  than  if  he  were  suddenly 
to  leave  it  off.  We  cannot  at  present  explain  this  result,  al- 
though it  is  quite  analogous  to  the  effect  of  other  narcotics  on 
persons  who  have  been  accustomed  to  their  use.  The  opium- 
eater  can  neither  work,  nor  eat,  nor  sleep,  if  his  opium  be  de- 
nied him  ;  he  is  ^  strengthened '  by  the  opium.  But  a  man  who 
is  not  accustomed  to  a  narcotic  is  most  certainly  not  rendered 
more  fit  for  work  by  taking  it. 

The  uselessness,  if  not  harmfulness,  of  even  moderate  doses 
of  alcohol  rests  on  better  evidence  than  scientific  deductions 
and  experiments.  In  connection  with  the  sanitation  of  armies, 
thousands  of  experiments  upon  large  bodies  of  men  have 
been  made,  and  have  led  to  the  result  that,  in  peace  and  war, 
in  every  climate,  in  heat,  cold,  and  rain,  soldiers  are  better  able 
to  endure  the  fatigues  of  the  most  exhausting  marches  when 
they  are  not  allowed  any  alcohol  at  all.^  A  similar  result  is 
observed  in  the  case  of  the  navies,  and  on  thousands  of  mer- 
chant vessels  belonging  to  England  and  America,  which  put  to 
sea  without  a  drop  of  alcohol.  Most  whalers  are  manned  by 
total  abstainers. 

That  mental  exertions  of  all  kinds  are  better  undergone 
without  alcohol  is  generally  admitted  by  most  people  who  have 
made  the  trial.  Alcohol  then  makes  no  one  stronger ;  it  only 
deadens  the  feeling  of  fatigue. 

One  of  the  disagreeable  sensations  which  alcohol  diminishes 
is  that  of  boredom.  This  feeling  is,  however,  like  the  sensation 
of  fatigue,  one  of  the  arrangements  for  self-regulation  which 
the  organism  possesses.  Just  as  the  feeling  of  fatigue  makes 
us  rest,  so  the  feeling  of  boredom  encourages  us  to  exertion, 
without  which  nerve  and  muscle  atrophy.  It  is  interesting  to 
observe  what  curious  means  a  lazy  and  empty-headed  man 
adopts  in  order  to  be  free  from  the  demon  of  boredom  without 
making  personal  exertion.  It  drives  him  without  rest  from 
place  to  place,  to  this  company  and  that,  from  one  distraction 
to  another.     But  all  these  attempts   to  escape  from  himself 

^  See  A.  Baer,  "Der  Alkoholismus,"  pp.  103-108:  Berlin,  1878.  References 
to  the  original  works  are  given  here. 


120  liECTUEE   IX 

would  be  in  vain,  and  the  bulk  of  mankind  would  be  driven  to 
exercise  their  brain  and  muscles  in  some  way  or  another, 
in  order  to  obtain  the  feeling  of  rest  and  satisfaction  and  to 
lose  their  sense  of  tedium,  were  it  not  for  alcohol.  Alcohol 
frees  them  easily  and  agreeably  from  this  demon.  A  drinker 
is  never  conscious  of  his  own  emptiness.  He  wants  no  inter- 
ests and  ideas ;  he  has  the  comfort  and  satisfaction  of  narcosis. 
There  is  nothing  so  dangerous  to  the  development  of  a  man, 
nothing  which  so  undermines  his  character,  nothing  which  so 
surely  destroys  the  remaining  energy  he  is  capable  of,  as  the 
continual  deadening  of  the  sense  of  tedium  by  means  of 
alcohol. 

Another  point  which  is  adduced  in  favor  of  alcoholic  drinks 
is  that  they  slow  metabolic  processes.  It  is  true  that  a  slight 
diminution  in  the  excretion  of  nitrogen,  and  consequently  of 
proteid  decomposition,  is  observed  after  moderate  doses  of  alco- 
hol.^ But  it  is  difficult  to  understand  why  this  should  be  made 
a  reason  for  recommending  alcoholic  drinks.  Why  should  we 
wish  to  diminish  the  metabolism  of  the  body  ?  Is  not  meta- 
bolism, or  the  breaking  down  of  the  tissues,  the  source  of  all  our 
energy  ?  The  intensity  of  this  metabolism,  this  conversion  of 
potential  into  kinetic  energy,  is  constantly  regulated  by  a  com- 
plicated nervous  mechanism,  which  now  acts  in  an  inhibitory, 
now  in  an  accelerating  direction,  according  to  the  requirements 
of  the  various  organs.  To  interfere  with  this  self-controlling 
mechanism  by  the  action  of  poisonous  substances  can  hardly  be 
wise,  since  we  are  almost  entirely  in  ignorance  concerning  its 
intimate  character.  What  means  have  we  of  judging  whether 
the  metabolism  is  too  quick  or  too  slow  ? 

Moreover  the  latest  and  most  accurate  researches  on  man 
have  failed  to  show  any  economy  of  proteid  as  the  result  of  the 
injection  of  alcohol.^  Among  these  investigations  the  minutely 
accurate  experiments  of  Miura  upon  himself  are  especially 
worthy  of  mention.  This  observer,  after  bringing  himself  into 
a  condition  of  nitrogenous  equilibrium  on  a  diet  of  fat  and 
carbohydrate,  replaced  for  a  few  days  a  portion  of  the  carbo- 
hydrate by  an  equivalent  quantity  of  alcohol.  He  found  that, 
on  these  days,  there  was  a  rise  in  the  excretion  of  nitrogen, 
which  was  as  great  as  on  other  days  when  a  portion  of  the 

'  A.  P.  Fokker,  "  Nederlandsch  Tijdschrift  voor  Geneeskunde,"  p.  125 :  1871  ; 
Imm.  Munk,  Verh.  der  Physiol.  Ges.  zu  Berlin:  Jan.  3, 1879  ;  L.  Reiss,  Zeitschr. 
f.  klin.  Med.,  vol.  ii.  p.  1 :  1880. 

2  Parkes,  Proc.  Roy.  Soc,  vol.  xx.  p.  402  :  1872.  H.  Keller  (Bunge's  labora- 
tory), Zeitschr.  f.  physiol.  CAem.,  vol.  xiii.  p.  128 :  1888.  Stammreich,  "  Ueb.  d. 
Einfluss  d.  Alkohols  auf  d.  Stoffwechsel  d.  Menschen,"  Dissert.:  Berlin,  1891. 
K.  Miura,  Zeitschr.  f.  klin.  Med.,  vol.  xx.  p.  137  :  1892. 


SUBSIDIARY    ARTICLES    OF    DIET  121 

'carbohydrate  was  omitted  without  any  corresponding  food  to 
take  its  place.  He  came  to  the  conclusion  therefore  that  alco- 
hol had  no  influence  on  proteid  disintegration,  and  that  it  could 
not  replace  carbohydrate  as  a  sparer  of  proteid. 

In  large  doses  alcohol  increases  instead  of  diminishing  the 
excretion  of  nitrogen.^  In  this  respect  it  resembles  certain 
powerful  poisons,  especially  phosphorus  and  arsenic,  which 
cause  increase  in  the  excretion  of  nitrogen,  but  at  the  same 
time  diminish  the  amount  of  oxygen  taken  up  and  carbonic 
acid  excreted,  and  consequently  produce  fatty  degeneration  of 
various  organs.  It  appears  that  these  poisons  give  rise  to  the 
production  of  fat  from  proteid ;  the  nitrogen,  with  a  small 
quantity  of  the  carbon,  is  separated  from  the  proteid  molecule, 
and  the  residue,  free  from  nitrogen,  is  stored  up  in  the  tissues 
as  fat.  We  shall  have  to  consider  this  process  in  greater  de- 
tail in  a  later  section  (Lecture  XIV.).  Possibly  the  fatty  de- 
generation of  the  organs  sometimes  observed  in  drunkards  is 
to  be  referred  to  a  similar  action.  But  unfortunately  the  ex- 
periments hitherto  made  have  not  decided  whether  the  con- 
sumption of  alcohol  has  any  influence  on  the  elimination  of 
carbonic  acid.^ 

It  is  commonly  thought  that  alcoholic  drinks  act  as  aids  to 
digestion.  In  reality  it  would  appear  that  the  contrary  is  the 
case.  Any  one  may  make  the  observation  on  himself,  that  a 
meal  without  alcohol  is  more  quickly  followed  by  hunger  than 
when  alcohol  is  taken.  The  inhibitory  influence  of  alcohol  on 
digestion  has  been  observed  on  a  patient  with  a  gastric  fistula,^ 
on  several  other  persons  by  the  aid  of  the  stomach-pump,*  and 
by  means  of  numerous  other  experiments.^ 

Up  to  this  point  I  have  chiefly  considered  the  action  of 
alcohol  on  persons  who  are  usually  called  moderate  drinkers. 
To  describe  the  ultimate  consequences  of  excessive  drinking 
can  hardly  come  within  the  scope  of  these  lectures.  It  may  be 
mentioned,  however,  that  the  misuse  of  alcoholic  drinks  causes 

^  Imm.  Munk,  loc.  cit. 

2  The  oft-quoted  experiments  of  Boeck  and  Bauer  allow  of  no  definite  con- 
clusion, as  the  duration  of  the  experiments  was  too  short  {Zeitschr.  f.  Biolog., 
vol.  X.  p.  361 :  1874).  The  same  is  still  more  applicable  to  the  experiments  of 
Wolfers  {Arch.  f.  d.  gesam.  Physiol.,  vol.  xxxii.  p.  222:  1883).  Zuntz  and 
Berdez,  Du  Bois'  Arch.,  p.  178:  1887.  J.  Geppert,  Arch.  f.  exper.  Path.  u. 
Pharm.,  vol.  xxii.  p.  367 :  1887.  N.  Simanowski  and  C.  Schoumoff  have  shown 
that  absorption  of  alcohol  diminishes  the  oxidation  of  benzol  into  phenol 
(Pfliiger's  ^rcA.,  vol.  xxxiii.  p.  251 :  1884).  j 

3  F.  Kretschy,  Deutsch.  Arch.  f.  klin.  Med.,  vol.  xviii.  p.  527:  1876. 

4  W.  Büchner,  ibid.,  vol.  xxix.  p.  537  :  1881. 

^Emil  Schütz,  Prager  med.  Wochenschr., 'No.  20:  1885;  Bikfalvi,  Maly's 
Jahresher.  f.  Thier  Chemie,  p.  273 :  1885 ;  Massanori  Ogata,  Arch.  f.  Hygiene, 
vol.  iii.  p.  204:  1885  ;  Klikowiez,  Virchow's  Arch.,  vol.  cii.  p.  360:  1885. 


122  LECTURE    IX 

a  whole  liost  of  diseases ;  that  no  organ  of  our  body  remains 
free  from  its  injurious  action.^  It  is  also  apparently  certain 
that  from  70  to  80  per  cent,  of  crime,  and  from  10  to  40  per 
cent,  of  the  suicides  in  most  civilized  countries,  are  to  be  as- 
cribed to  alcohol. 

We  must  however  strictly  discriminate  between  the  use  of 
alcohol  as  a  luxury  and  an  article  of  diet,  and  its  use  as  a 
medicine.  In  the  opinion  of  many  practitioners,  it  is  indis- 
pensable as  a  medicine.  It  is  precisely  its  paralyzing  prop- 
erties which  render  it  valuable  in  this  case.  It  is  a  mild 
anesthetic,  and  acts  as  a  sedative  by  diminishing  abnormally 
increased  reflex  irritability.  Alcohol  is  further  used  as  an 
antipyretic ;  but  proof  of  its  value  in  this  capacity  is  still 
lacking. 

It  is  evident  to  every  reasonable  being  that  alcoholic  drinks 
can  only  be  prescribed  for  acute  diseases,  and  should  never  be 
allowed  in  chronic  disorders  for  the  same  reason  that  chloral 
and  morphia  are  not  given  in  such  cases,  unless  indeed  to  com- 
pass euthanasia.  There  can  be  no  doubt  that  many  medical 
men  are  guilty  of  much  harm  in  recommending  the  use  of 
alcohol,  and  there  is  hardly  a  single  drunkard  who  does  not 
adduce  the  authority  of  some  medical  man  or  other  in  support 
of  his  failing.  It  is .  in  the  highest  degree  desirable  that 
alcohol  should  be  replaced  by  some  other  drug  even  in  those 
cases  where  its  use  seems  to  be  indicated,  since  it  is  hardly 
possible  to  get  rid  of  the  deeply  rooted  superstition  as  to  the 
strengthening  and  stimulating  effect  of  alcohol,  so  long  as  it 
continues  to  be  constantly  employed  as  a  therapeutic  agent. 
We  may  hope  that  the  temperance  hospitals  which  have  been 
founded  in  England  and  America,  and  where  absolutely  no 
alcohol  is  given,  may  soon  flirnish  sufficient  statistics  to  prove 
once  and  for  all  that  alcohol  is  not  indispensable  in  medical 
practice. 

Tea  and  coffee  are  much  less  likely  to  cause  ill  effects 
than  alcoholic  liquors.  They  exert  no  paralytic  influence  ;  on 
the  contrary,  they  are  helpfiil  in  both  mental  and  physical 
exertions.  In  their  use  there  is  but  little  danger  of  excess. 
It  is  true  that  they  occasionally  disagree  with  certain  people, 

^  On  this  point  see  Legrain,  "Heredite  et  Alcoholisme,"  Paris,  1891; 
Laurent,  "  Les  habitues  des  Prisons  de  Paris,"  Paris,  1890 ;  P.  Garnier,  "La  Folie 
ä  Paris,"  Paris,  1890;  Bourneville,  "  Progres  medical,"  p.  21:  1897.  J.  Sendt- 
ner,  "Ueb.  Lebensdauer  u.  Todesursache  b.  d.  Biergerwerben.  Ein  Beitrag  z. 
jEtioIogie  d.  Herzerkrankungen,"  München,  1891 ;  Demme,  "  Ueb.  d.  Einfluss 
d.  Alkohols  auf.  d.  Organismus  d.  Kindes,"  Stuttgart,  1891 ;  A.  Strümpell,  "  Ueb. 
d.  Alkoholfrage  V.  serztlichen  Standpunkte  aus.,"  Berl.  Hin.  Woch.,  p.  933: 
1893. 


SUBSIDIARY    ARTICLES    OF    DIET  123 

especially  if  token  in  too  large  quantities ;  and  their  long-con- 
tinued misuse  may  cause  illness.  But  in  these  cases  there  is 
but  little  difficulty  in  inducing  the  people  so  affected  to  abstain. 
A  patient  who  is  recommended  seriously  to  refrain  from  taking 
too  much  tea  generally  does  so ;  a  patient  who  takes  too  much 
alcohol  does  not  easily  give  it  up.  A  man  rarely  becomes  the 
slave  of  coffee  or  tea,  and  excessive  drinking  of  tea  and  coffee 
never  produces  a  state  of  moral  irresponsibility,  nor  leads  to  the 
commission  of  crime. 

Tea  and  coffee  contain,  as  is  well  known,  an  active  principle 
common  to  both,  caffein  or  thein,  which  is  closely  related  to 
xanthin,  a  crystalline  substance  rich  in  nitrogen,  which  enters 
in  small  quantity  into  all  our  tissues.  We  shall  study  xanthin 
in  connection  with  the  chemistry  of  the  urine  (Lecture  XX.). 
Caffein  is  xanthin  with  three  methyl  groups  introduced  into  its 
molecule,  and  it  can  be  artificially  prepared  from  these  constit- 
uents.^ 

It  is  a  very  remarkable  and  surprising  fact  that  people  of 
the  most  different  races,  in  all  parts  of  the  world,  have 
succeeded  in  discovering  caffein  in  the  most  varied  plants. 
The  Arabs  found  it  in  the  coffee  bean ;  the  Chinese  in  tea ; 
the  natives  of  Central  Africa  in  the  cola  nut  (^Cola  acmninata)  ; 
those  of  South  Africa  in  bush  tea,  the  leaves  of  a  variety  of 
Cyclopia ;  the  natives  of  South  America  in  Paraguay  tea  [Ilex 
paraguayensis),  and  in  the  seeds  of  Paulinia  soi^bilis,  a  Brazilian 
creeper ;  the  Indians  of  North  America  in  Apalache  tea,  the 
leaves  of  several  varieties  of  ilex.  This  fact  is  the  more 
remarkable  as  caffein  can  be  detected  neither  by  its  taste  nor 
smell.  Also  interesting  is  the  close  relation  of  this  universally 
prized  luxury  to  one  of  the  constituents  of  our  tissues.  It  is 
possible  that  the  caffein  molecule,  in  consequence  of  its  similar 
constitution,  has  an  affinity  for  the  same  tissue-elements  in 
which  xanthin  is  found,  and  that  it  plays  an  analogous  though, 
in  consequence  of  its  more  complex  constitution,  a  modified 
part.  This  may  explain  the  stimulating  action  which  it  pos- 
sesses. 

Caffein  is  mostly  destroyed  in  the  tissues  of  our  body. 
Experiments  ^  conducted  in  Dragendorft's  laboratory  in  Dorpat 

■^  Emil  Fischer,  Liebig^'s  Annal.,  vol.  ccxv.  p.  253  :  1882. 

^  Rich.  Schneider,  "  Ueber  das  Schicksal  des  Caffeins  und  Theobromins  im 
Thierkörper,  nebst  Untersuchungen  über  den  Nachweis  des  Morphins  im  Harn," 
Dissert.:  Dorpat,  1884.  Schutzkwer  ("Das  CalFein  u.  sein  Verhalten  im  Thier- 
körper," Dissert.:  Königsberg,  1883)  found  that,  of  0.2  grm.  of  caffein  sub- 
cutaneously  injected  into  a  dog,  only  0.012  reappeared  in  the  urine.  Maly  and 
Andreasch  ("Studien  über  Caffein  und  Theobromin,"  3Ionatshefte  der  Chem., 
May :  1883)  found  that,  of  0.1  grm.  administered  internally  to  a  small  dog, 
0.066  reappeared  in  the  urine. 


124  LECTUEE    IX 

have  shown  that  of  the  amount  of  caffein  which  is  absorbed  as 
the  result  of  ordinary  tea  and  coflPee  drinking — a  cup  of  coffee 
contains  about  0.1  grm.  caffein,  and  the  same  amount  is  con- 
tained in  from  2  to  10  grms.  dry  tea  leaves — none  passes  into 
the  urine.  Caffein  can  be  detected  in  the  urine  when  0.5  grm. 
caffein  has  been  taken.  Caffein  has  no  influence  on  the  proteid 
metabolism  of  the  organism.  Voit  ^  has  shown  by  carefal  ob- 
servation that  the  amount  of  nitrogen  excreted  is  neither  in- 
creased or  diminished  by  the  use  of  caffein. 

This  is  not  the  place  to  give  a  detailed  account  of  the  various 
modes  of  action  of  caffein  ;  I  must  refer  you  to  works  on  phar- 
macology. In  addition  to  this  common  constituent,  tea  contains 
ethereal  oils,^  and  in  coffee  certain  aromatic  substances  are 
formed  as  the  result  of  roasting ;  hence  the  difference  of  taste 
and  action  of  these  substances. 

A  substance  chemically  closely  allied  and  of  similar  action 
to  caffein  is  found  in  the  cocoa  bean.  This  is  theobromin,  a 
dimethyl-xanthin.  In  the  seeds  of  Paulinia  soi'bilis,  from 
which  guarana  paste,  much  liked  in  South  America,  is  pre- 
pared, both  these  substances  are  united.  Filehne  ^  has  recently 
studied  the  action  of  theobromin  on  muscle  and  on  the  central 
nervous  system,  and  compared  it  with  the  action  of  xanthin  and 
of  caffein.  He  has  arrived  at  the  interesting  result  that  the 
chemical  series,  caffein  (trimethyl-xanthin),  theobromin  (di- 
methyl-xanthin), and  xanthin  present  a  corresponding  series 
in  their  pharmacological  action.  A  monomethyl-xanthin  is  at 
present  unknown.  The  cocoa  bean  is  not  only  a  luxury,  but 
also  very  valuable  as  nutriment ;  it  contains  half  its  weight  of 
fat,  and  in  addition  about  12  per  cent,  of  proteid.  Chocolate 
might  be  very  serviceable  for  military  purposes.  It  is  hardly 
possibly  to  carry  food  in  a  more  concentrated  form  than  in 
chocolate. 

Bouillon  and  extract  of  meat,  which  is  bouillon  evapo- 
rated to  a  semi-solid  consistence,  afford  the  most  harmless  sub- 
sidiary aliments.  The  extractives  of  meat  do  not,  so  far  as 
is  known,  exert  the  slightest  narcotic  influence.  They  act 
entirely  on  taste  and  smell.  This  agreeable  effect  can  hardly 
be  overestimated,  but  we  must  guard  against  supposing  that 

^  C.  Voit,  "  Unt.  üb.  d.  Einfl.  des  Kochsalzes,  des  Kaffees  und  der  Muskel- 
bewegungen auf  den  Stoffwechsel,"  pp.  67-147 :  München,  1860. 

2  A.  Koch  and  E.  Krtepelin  ("Psycholog.  Arb.,"  vol.  i.  p.  378:  1895)  have 
investigated  the  effects  of  these  ethereal  oils  and  of  the  thein  separately,  and  have 
found  that  the  pleasant  results  of  tea  drinking  must  be  referred  to  both  con- 
stituents. 

3  Wilhelm  Filehne,  Du  Bois'  Arch.,  p.  72  :  1886.  A  summary  of  the  earlier 
literature  will  also  be  found  here.  Comp,  also  Kobert,  Arch,  f,  exper.  Path.  u. 
Fharm.,  vol.  xv.  p.  22  :  1882. 


SUBSIDIARY    ARTICLES    OF    DIET  125 

meat  bouillon  possesses  strengthening  and  nourishing  properties. 
In  regard  to  this,  the  most  delusive  notions  are  entertained,  not 
only  by  the  general  public,  but  also  by  medical  men. 

Until  quite  recently,  the  opinion  was  held  that  bouillon  con- 
tained the  most  nutritive  part  of  meat.  There  was  a  conftised 
idea  that  a  minute  quantity  of  material — a  plateful  of  bouillon 
can  be  made  from  a  teaspoon  ful  of  meat-extract — could  yield 
an  effectual  source  of  nourishment,  that  the  extractives  of  meat 
were  synonymous  with  concentrated  food. 

Let  us  inquire  what  substances  could  render  bouillon  nu- 
tritious. The  only  article  of  food  which  meat  yields  to  boiling 
water  is  gelatin.  It  is  well  known  that  proteid  is  coagulated, 
on  boiling,  the  glycogen  of  meat  is  rapidly  converted  into 
sugar,  and  this  again  into  lactic  acid.  The  quantity  of  gelatin 
is  moreover  very  small ;  for  a  watery  solution  which  contains 
only  1  per  cent,  of  gelatin  forms  a  jelly  on  cooling.  This 
certainly  occurs  in  very  strong  soups  and  gravies,  but  never 
in  bouillon.  Bouillon  therefore  contains  much  less  than  1  per 
cent,  of  gelatin.  In  preparing  extract  of  meat,  the  quantity 
of  gelatin  is  reduced  as  much  as  possible,  because  it  is  in  a 
high  degree  liable  to  putrefactive  changes,  and  therefore  likely 
to  interfere  with  the  preservation  of  the  preparation.  The 
other  constituents  of  bouillon  are  decomposition  products  of 
food-stuifs — products  of  the  oxidations  and  decompositions  which 
take  place  in  the  animal  organism.  They  cannot  be  regarded 
as  nutritious,  because  they  are  no  longer  capable  of  yielding 
any  kinetic  energy,  or  at  most  such  a  small  amount  that  it  is  of 
no  importance  whatever. 

Nevertheless,  until  the  most  recent  times,  creatin  and 
Creatinin,^  which  are  among  the  chief  constituents  of  meat- 
extract,  were  regarded  as  the  source  of  energy  in  muscle. 
This  assertion  was  shown  to  be  untrue  by  the  researches  of 
Meissner^  and  of  Voit,^  who  proved  conclusively  that  the 
whole  of  the  creatin  and  Creatinin  taken  into  the  body  is  ex- 
creted unchanged  in  the  urine  twenty-four  hours  after  its  ab- 
sorption. A  material  which  is  neither  oxidized  nor  decomposed 
cannot  form  a  source  of  energy,  apart  from  the  fact  that  the 
quantity  of  creatin  and  Creatinin  in  bouillon  is  so  small  that 
it  could  not  possibly  be  regarded  as  the  source  of  muscular 
energy. 

^  For  the  chemical  constitution  and  the  physiological  significance  of  these 
compounds,  see  Lecture  XIX. 

2  G.  Meissner,  Zeitschr.  /.  rat.  Med.,  vol.  xxiv.  p.  97  :  1865  ;  vol.  xxvi.  p.  225  : 
1866  ;  and  vol.  xxxi.  p.  283  :  1868. 

3  C.  Voit,  Zeitschr.  f.  Biolog.,  vol.  iv.  p.  Ill  :  1868. 


126  LECTUEE   IX 

It  has  fiirther  been  asserted  that  the  addition  of  extract 
of  meat  increases  the  nutritive  value  of  vegetable  food,  and 
gives  the  latter  the  same  value  as  fresh  meat.  This  assertion 
has  also  been  refuted  by  Voit  and  his  pupils/  who  have  shown 
by  experiments  made  on  man  and  on  animals,  that  the  un- 
favorable conditions  of  assimilation  which  characterize  vege- 
table food  are  not  improved  by  the  addition  of  extract  of 
meat. 

Finally,  the  attempt  has  been  made  to  attach  a  value  as  a 
food  to  extract  of  meat,  in  consequence  of  the  considerable 
quantity  of  salts,  "nutritive  salts,"  which  it  contains.  But, 
as  I  have  already  explained,  there  is  no  lack  of  salts  in  our 
food,  but  always  an  excess.  Even  for  the  growing  organism 
there  is  only  one  inorganic  constituent  which  could  be  deficient, 
i.  e.,  lime.  But  there  is  very  little  lime  in  meat-extract ;  the 
ash  contains  only  0.23  per  cent.  CaO.^  No  one  would  be 
likely  to  eat  more  than  30  grms.  of  meat-extract,  which  repre- 
sents the  amount  obtained  from  1  kgrm.  of  meat,  and  contains 
only  0.015  grm.  of  lime — that  is,  the  same  quantity  as  is  con- 
tained in  10  c.cms.  of  cow's  milk. 

We  must  therefore  conclude  that  meat-extract  can  only  be 
looked  upon  as  a  pleasant  adjunct  to  food.  It  is  asserted  even 
at  the  present  time  that  extract  of  meat  acts  in  the  same  stimu- 
lating and  refreshing  manner  as  tea  and  coffee  undoubtedly  do ; 
but  up  to  this  date  no  direct  action  of  extract  of  meat  on  muscles 
or  nerves  has  been  proved.  The  only  investigation  in  this 
direction  is  due  to  Kemmerich,^  who  lays  stress  on  the  large 
amount  of  potassium  salts  contained  in  extract  of  meat,  and 
asserts,  as  the  result  of  his  experiments,  that  they  exert,  in 
small  doses  a  stimulating,  in  large  doses  a  depressing,  effect  on 
the  action  of  the  heart.  He  therefore  warns  against  immoderate 
use  of  the  extract  of  meat. 

So  far  as  the  potassium  salts  are  concerned,  the  following  is 
really  the  case.*  The  stimulating  action  on  the  heart  which 
Kemmerich  observed  was  in  no  way  due  to  the  potassium  salts, 
but  simply  to  the  fact  that  he  used  rabbits  for  his  experiments. 
Being  very  timid  animals,  the  injection  of  almost  any  in- 
different substance,  such  as'a  solution  of  sugar  or  of  common 
salt,  may  easily  produce  a  decided  increase  in  the  rate  of  the 

1  Ernst  Bischoff,  Zeitschr.  /.  Biolog.,  vol.  v.  p.  454  :  1869  ;  and  C.  "Voit,  Zeit- 
achr.f.  Biolog.,  vol.  iv.  pp.  359,  360:  1870. 

2  G.  Bunge,  Pflüger's  Arch.,  vol.  iv.  p.  238  :  1871. 
^  Kemmerich,  Pflüger's  Arch.,  vol.  ii.  p.  49  :  1869. 

■*  G.  Bunge,  Pflüger's  Arch.,  vol.  iv.  p.  235  :  1871 :  and  Zeitschr.  f.  Biolog., 
vol.  ix.  p.  130  :  1873.  Lehmann  has  recently  confirmed  my  results  (see  Arch.  f. 
Hygiene,  vol.  iii.  p.  249  :  1885). 


SUBSIDIARY    ARTICLES    OF    DIET  127 

pulse.  The  mere  passage  of  the  stomach  sound  is  sufficient  to 
have  this  effect.  By  large  numbers  of  experiments  both  on  dogs 
and  on  the  human  subject,  I  have  convinced  myself  that  the  in- 
troduction of  potassium  salts  into  the  stomach  is  never  followed 
by  the  slightest  acceleration  of  the  pulse. 

The  paralyzing  influence  on  the  heart,  observed  by  Kem- 
merich,  is  due  to  his  having  used  an  amount  of  potash  salts 
quite  out  of  proportion  to  the  weight  of  the  rabbit.  To  give  a 
rabbit  of  1000  grms.  body  weight,  5  grms.  of  potash  salts  is 
the  same  as  giving  a  man  300  grms.  An  additional  factor  in 
the  case  of  a  rabbit  is  that  it  is  unable  to  vomit.  It  is  im- 
possible to  produce  any  influence  on  the  heart  of  the  dog, 
since  an  excessive  dose  of  potassium  salts  is  promptly  followed 
by  vomiting.  I  have  found  by  numerous  experiments  that  the 
maximum  dose  (about  12  grms.),  which  can  be  taken  without 
causing  vomiting,  is  quite  without  influence  on  the  action  of 
the  heart.  In  cases  where  poisoning  has  actually  ensued  as  the 
result  of  overdoses  of  potassium  salts,  death  has  been  due  to  a 
gastro-enteritis,  and  not  to  any  effect  upon  the  heart.  Potas- 
sium salts  have  a  local  corrosive  effect.  The  gastric  mucous 
membrane  of  animals  into  whom  salts  of  potassium  have  been 
injected,  is  always  hyperemic,  and  sometimes  covered  with  ec- 
chymoses.  If  the  potassium  salts  are  given  in  a  very  concen- 
trated form,  especially  in  powder,  gastritis,  with  a  fatal  result, 
may  be  produced. 

In  all  animals  paralysis  of  the  heart  follows  rapidly,  if  the 
solution  of  potassium  salts  be  injected  directly  into  the  blood. 
As  the  result  of  my  own  experience,  I  have  convinced  myself 
that  when  0.1  grm.  KCl  is  injected  into  a  medium-sized  dog, 
an  almost  immediate  arrest  of  the  heart  follows.  Subcutaneous 
injection  of  potassium  salts  also  causes  cessation  of  the  cardiac 
beat.  But  paralysis  of  the  heart  is  never  preceded  by  accelera- 
tion, but  always  by  a  slowing  of  the  pulse. 

It  is  hardly  necessary  to  recur  to  experiment  in  order  to 
show  how  entirely  umocuous  salts  of  potassium  are  when 
taken  by  the  mouth ;  it  has  only  to  be  borne  in  mind  how 
large  a  quantity  is  constantly  consumed  with  vegetable  food. 
I  have  already  noticed  the  fact  that  a  man  who  lives  chiefly  on 
potatoes  absorbs  over  50  grms.  of  potash  salts  in  the  course  of 
a  day. 

The  potash  salts,  therefore,  which  occur  in  bouillon,  cannot 
produce  any  effect  on  the  heart,  neither  small  doses  stimulating 
it,  nor  large  ones  paralyzing  it.  But  even  if  we  could  admit 
the  exciting  action  of  potassium  salts,  it  would  be  difficult  to 
see  why  we  should  take  bouillon  on  account  of  the  potash  it 


128  LECTUEE    IX 

contains,  since  we  could  get  much  more  with  almost  any  other 
form  of  food.  Five  grammes  of  extract  of  meat  will  make  a 
plateful  of  bouillon,  and  they  only  contain  0.5  grm.  potassium, 
the  same  quantity  as  in  a  small  potato. 

We  see  then  that  the  only  experiment  which  has  been 
hitherto  attempted  to  demonstrate  the  stimulating  influence  of 
extract  of  meat  has  not  been  successful. 

It  has  frequently  been  asserted  that  the  organic  constituents 
of  meat-extract  exert  an  influence  on  the  muscular  nervous 
system,  but  never  on  sufficient  ground.  As  regards  creatin 
and  Creatinin  in  particular,  Voit^  has  given  details;  he  found 
that  6.3  grms.  creatin  and  8.6  grms.  Creatinin  given  to  a  dog 
produced  no  symptoms  whatever.  More  recently  Kobert  ^  has 
endeavored  to  demonstrate  an  action  of  creatin  on  muscle. 
The  experiments  were  conducted  on  frogs,  and  excessive  doses 
of  creatin  used ;  but  the  result  was  ambiguous.  Human 
muscle  could  hardly  be  influenced  by  the  minute  quantity 
(about  0.2  grm.)  of  creatin  contained  in  an  ordinary  plateful  of 
soup.  This  can  be  deduced  ä  priori,  quite  apart  from  the 
observations  of  Voit.  Our  muscles  contain  about  3  per  1000 
creatin.^  The  whole  muscular  system  of  an  adult  man,  which 
amounts  to  about  30  kgrms.,  contains  consequently  about  90  grms. 
It  is  also  found  in  the  nervous  system  and  in  the  blood.  With 
regard  to  the  small  quantity  of  creatin  which  is  taken  in 
bouillon,  absorbed,  and  at  the  same  time  rapidly  excreted  by 
the  kidneys,  we  are  uncertain  whether  it  ever  reaches  the 
muscles  at  all.  And  even  if  a  small  quantity  should  do  so,  it 
can  hardly  be  of  any  importance,  when  we  know  that  the 
muscles  already  contain  90  grms.  of  creatin. 

That  some  other  organic  constituent  of  meat-extract  may 
produce  an  effect  on  the  muscular  or  nervous  system,  must  be 
admitted  to  be  remotely  possible ;  at  present  it  is  in  no  way 
proved.  We  know,  with  regard  to  bouillon,  absolutely  no  more 
than  that  it  tastes  and  smells  agreeably.  This  fact,  however, 
suffices  to  explain  all  the  ^  enlivening '  and  '  strengthening ' 
virtues  which  common  experience  attributes  to  extract  of  meat 
and  bouillon,  and  to  recommend  them  as  valuable  and  pleasant 
accessories  of  our  food. 

1  C.  Voit,  "  Ueber  die  Entwicklung  der  Lehre  von  der  Quelle  der  Muskel- 
kraft," p.  39  :  1870 ;  or  Zeitschr.  f.  Biolog.,  vol.  vi.  p.  343  :  1870. 

2  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xv.  p.  56  :  1882. 

3  Fr.  Hofmann,  Zeitschr.  f.  Biolog.,  vol.  iv.  p.  82  :  1868 ;  M.  Perls,  Deutsch. 
Arch.  f.  Hin.  Med.,  vol.  vi.  p.  243  :  1869. 


LECTURE  X 


SALIVA    AND    GASTRIC   JUICE 

We  have  in  previous  chapters  become  acquainted  with  the 
various  food-stuifs,  and  we  must  now  trace  their  course  through 
our  bodies,  and  the  gradual  changes  which  they  undergo. 

The  first  fluid  with  which  the  food  comes  in  contact  on 
being  introduced  into  the  alimentary  canal,  is  the  saliva,^ 
which  is  well  known  to  be  the  secretion  of  three  larger  pairs 
of  glands,  and  of  the  small  glands  in  the  mucous  membrane  of 
the  mouth.  The  amount  of  saliva  formed  in  the  course  of 
twenty-four  hours  is  very  considerable,  and  according  to  an 
approximate  estimate  of  Bidder  and  Schmidt,^  is  about  1500 
c.cms.  This  secretion  might  therefore  be  expected  to  play  an 
important  part  in  the  processes  of  digestion,  but  it  has  not  yet 
been  found  that  it  does  so.  The  saliva  has  no  efi'ect  on  most 
articles  of  diet ;  starch  alone  is  converted  by  its  means  into 
dextrin  and  sugar.  But  even  this  action  is  very  inconsider- 
able ;  it  is  nothing  compared  with  the  powerful  action  of  the 
pancreatic  juice  in  breaking  up  starch.  The  period  during 
which  the  saliva  acts  is  of  very  short  duration.  The  salivary 
ferment  can  only  operate  fully  on  starch  under  the  faintly 
alkaline  reaction  which  belongs  to  normal  saliva.  This  action 
is  immediately  enfeebled  or  entirely  neutralized  by  the  acid 
gastric  juice.^  Thus  only  a  very  small  portion  of  the  starch 
consumed  is  split  up  by  the  salivary  ferment.     But  the  saliva 

^  The  processes  of  secretion  in  the  salivary  glands  have  been  more  closely 
investigated  by  Bernard,  Ludwig,  and  Heidenhain  than  those  in  any  other 
glands,  and  the  results  of  these  investigations  are  among  the  most  important 
achievements  of  modern  physiology.  But  these  works  have  thrown  no  light 
upon  the  chemical  processes  in  glandular  activity.  I  therefore  think  it  better  to 
pass  them  over,  especially  as  they  are  adequately  described  in  all  text-books  of 
physiology. 

2  Bidder  and  Schmidt,  "  Die  Verdauungssäfte  und  der  Stoffwechsel,"  p.  14: 
Mitau  and  Leipzig,  1852. 

^  O.  Hammarsten,  Panum's  Report  in  the  Jahresbericht  über  die  Leistungen 
der  ges  Medicin.,  Jahrg.  vi.  vol.  i.:  1871.  [Cannon  has  shown  however  that  at 
least  half  an  hour  may  elapse  before  the  food  taken  in  with  the  meal  is  thor- 
oughly mixed  with  the  gastric  juice.  During  this  time  the  food  remains  in  the 
fundus  of  the  stomach,  and  in  its  inner  portions  salivary  digestion  can  go  on  un- 
checked.    (Amer.  Journ.  of  Physiol. ,  vol.  i.  p.  359:  1898.)] 

9  129 


130  liECTUEE    X 

of  some  mammals  has  not  even  this  slight  action,  as  in  the  case 
of  the  Carnivora,  where  for  teleological  reasons  it  might  be  ex- 
pected to  be  absent. 

As  saliva  is  very  abundantly  secreted  by  Carnivora,  it  is 
apparent  that  the  decomposition  of  starch  is  not  its  main  func- 
tion. 

It  was  hoped  that  by  extirpating  the  salivary  glands  of 
dogs,^  and  then  observing  what  disturbances  took  place  in  con- 
sequence, a  conclusion  might  be  arrived  at  as  to  the  significance 
of  saliva.  No  prejudicial  effects  were  detected,  although  it  was 
remarked  that  the  dogs  drank  more  water  than  usual  with  their 
accustomed  and  carefully  regulated  diet. 

It  appears  that  the  saliva  is  chiefly  of  importance  from  a 
mechanical  point  of  view.  It  moistens  the  food  in  the  mouth 
and  prepares  it  for  the  act  of  swallowing.  At  the  same  time 
the  mouth  is  kept  clean  by  the  constant  secretion.  If  particles 
of  food  were  allowed  to  remain  in  the  mouth,  the  acids  which 
would  be  formed  as  the  result  of  their  decomposition,  would 
injure  the  teeth  ;  this  is  prevented  by  the  mouth  being  continu- 
ally kept  moist  with  the  alkaline  saliva.  If  this  view  of  the 
use  of  saliva  is  correct,  we  should  expect  the  salivary  glands  of 
mammals  living  in  water  to  be  absent,  since  the  food  they  take 
is  always  sufficiently  moist,  and  the  cavity  of  the  mouth  is  con- 
stantly being  washed  out  by  water.  This  is  in  fact  the  case. 
The  Cetacea  lack  salivary  glands  entirely,  and  in  the  Pinnipedia 
they  are  only  rudimentary. 

In  the  stomach  the  food  meets  with  a  second  secretion,  the 
GASTRIC  JUICE,  distinguished  from  all  the  other  digestive  fluids 
by  its  acid  reaction.  This  acid  reaction  is  due  to  the  free  hy- 
drochloric acid.  The  proof  of  this  was  furnished  by  Carl 
Schmidt.^  He  determined  the  exact  quantity  of  the  chlorin 
and  of  all  the  bases,  potash,  soda,  lime,  magnesia,  oxid  of  iron, 
and  ammonia.  The  result  was  that,  after  allowing  enough  hy- 
drochloric acid  to  saturate  all  the  bases,  a  quantity  remained 
over  which  amounted  to  about  2.5  to  4  grms.  in  1  liter.  Carl 
Schmidt  determined,  in  addition,  the  amount  of  free  acid  by 
means  of  titration,  and  obtained  almost  exactly  the  same  num- 
bers as  in  the  case  of  the  determination  by  weight. 

If  we  now  inquire  into  the  significance  of  this  free  acid,  we 
find  that  most  writers  regard  it  as  subserving  the  digestion  of 
proteids.     Proteids,  and  gelatins,  which  are  closely  allied  to 

^C.  Fehr,  "Ueber  die  Exstirpation  sämmtlicher  Speicheldrüsen  beim 
Hunde,"  Dissert.:  Giessen,  1862. 

2  Bidder  and  Schmidt,  "  Die  Verdauungssäfte  und  der  Stoffwechsel,"  pp.  44, 
45  :  Mitau  and  Leipzig,  1852. 


SALIVA   AND   GASTRIC   JUICE  131 

them,  are  in  fact  the  only  food-stuffs  which  are  altered  by  the 
gastric  juice.  They  are  changed  into  peptones/  which  are  dis- 
tinguished from  proteids  and  gelatins  by  the  fact  that  they  no 
longer  retain  their  colloid  properties,  are  no  longer  coagulable, 
are  more  readily  diffusible  through  animal  membranes,  and  con- 
sequently appear  particularly  suited  for  absorption  into  the 
blood.  This  peptonizing  action  is  attributed  to  a  ferment  called 
pepsin.^  Pepsin  is  however  only  effectual  in  the  presence  of  a 
free  acid.  Hence  up  to  the  present  time  it  has  been  the  custom 
to  regard  free  acid  as  being  only  of  use  in  rendering  the  action 
of  pepsin  possible. 

But  we  cannot  be  content  with  this  explanation  ;  we  know 
that  the  pancreatic  ferment  acts  even  more  energetically  than 
the  gastric  juice,  and  that  it  is  most  efficacious  when  the  reac- 
tion is  faintly  alkaline.  Why  should  the  gastric  glands  have 
the  severe  labor  of  separating  free  hydrochloric  acid  from  the 
alkaline  blood,  if  the  organism  can  effect  its  purpose  by  much 
simpler  means — by  the  secretion  of  an  alkaline  fluid?  The 
free  acid  must  have  some  other  significance.  At  the  present 
day,  when  our  knowledge  of  putrid  fermentation  and  the  means 
of  combating  it  has  so  much  increased,  and  when  we  have  found 
that  free  mineral  acids  are  to  be  counted  among  the  most  effec- 
tual antiseptics,  it  is  not  unreasonable  to  attribute  this  function 
to  the  free  hydrochloric  acid  of  the  gastric  juice.  It  has  the 
duty  of  killing  the  microorganisms  which  reach  the  stomach 
with  the  food.  These  would  otherwise  set  up  processes  of  de- 
composition in  the  alimentary  canal,  and  thus  destroy  a  part  of 
the  food  before  its  absorption,  whilst  the  products  of  decomposi- 
tion would  produce  disagreeable  symptoms,  or  even,  as  a  cause 
of  disease,  endanger  life. 

N.  Sieber,^  in  Nencki's  laboratory  in  Berne,  determined  the 
strength  of  the  hydrochloric  acid  which  suffices  to  prevent  the 
development  of  putrefactive  organisms  in  substances  capable  of 
putrefaction,  and  arrived  at  the  following  results. 

If  50  grms.  finely  chopped  meat  were  put  into  an  open  flask 
with  300  c.cms.  of  a  0.1  per  cent,  solution  of  hydrochloric  acid, 
only  a  scanty  development  of  micrococci  and  bacilli  took  place 
in  twenty-four  hours.     After  forty-eight  hours  they  had  some- 

^  The  nature  and  significance  of  peptones  will  he  discussed  later  on  (see  Lec- 
tures XI.  and  XIII.). 

^  See  Lecture  X.  for  the  experiments  on  the  isolation  of  pepsin.  Besides 
pepsin,  another  ferment,  the  '  rennet  ferment,'  is  included  in  the  gastric  juice, 
and  this  causes  the  coagulation  of  milk  in  the  stomach.  Nothing  is  known  con- 
cerning the  physiological  import  of  this  coagulation.  I  therefore  omit  all  account 
here. 

^  N.  Sieber,  Journ.  f.  prakt.  Chem.,  vol.  xix.  p.  433 :  1879. 


132  LECTURE   X 

what  increased,  and  on  the  third  day  the  fluid  presented  a  dis- 
tinctly putrefactive  odor,  and  a  weakly  acid  reaction. 

When  the  experiment  was  made,  ceteris  paribus,  with  0.25 
per  cent,  hydrochloric  acid,  isolated  non-motile  organisms  were 
not  found  till  the  seventh  day,  and  pronounced  formation  of 
mould  not  until  the  ninth  day. 

In  a  third  experiment  carried  out,  ceteris  paribus,  with  0.5 
per  cent.  HCl,  "  no  trace  of  putrefaction "  appeared  until  the 
seventh  day. 

Miquel  ^  attained  the  same  result,  finding  that  from  0.2  to 
0.3  grm.  mineral  acid  was  sufficient  to  render  100  c.cms.  of 
bouillon  incapable  of  undergoing  putrefaction. 

In  the  gastric  juice  of  a  dog — obtained  from  a  gastric  fistula, 
and  from  which  all  admixture  with  saliva  had  been  prevented 
by  previous  ligature  of  all  the  salivary  ducts — C.  Schmidt^ 
found  in  eight  analyses,  from  0.25  to  0.42  per  cent.  HCl,  the 
mean  of  the  eight  analyses  being  0.33  per  cent.  Heidenhain  ^ 
found  in  the  secretion  of  the  glands  of  the  cardiac  end  of  the 
stomach,*  by  means  of  titration  in  thirty-six  cases,  from  0.46  to 
0.58,  as  a  mean  0.52  HCl  per  cent. 

In  Hoppe-Seyler's  laboratory,^  the  free  acid  contained  in  the 
undiluted  gastric  juice,  obtained  from  a  man  by  the  aid  of  the 
stomach-pump,  was  determined ;    0.3  per  cent.  HCl  was  found. 

We  thus  arrive  at  the  striking  result  that  the  quantity  of 
free  hydrochloric  acid  in  the  gastric  juice  exactly  corresponds 
to  the  quantity  which  is  necessary  to  prevent  the  development 
of  putrefactive  organisms.  This  coincidence  cannot  be  acci- 
dental. 

It  might  be  objected  to  this  that  the  gastric  juice  is  diluted 
by  the  saliva  and  the  food.  On  the  other  hand  it  must  be  re- 
membered that,  owing  to  the  constant  peristaltic  action  of  the 
stomach,  different  portions  of  its  contents  are  constantly  being 
brought  into  contact  with  the  secreting  wall,  and  consequently 
into  contact  with  hydrochloric  acid  of  the  strength  requisite  to 
kill  bacilli.  In  fact,  under  normal  conditions,  pronounced 
putrefactive  decomposition  never  occurs  in  the  stomach.  But 
if,  under  pathological  conditions,  the  secretion  should  be  inter- 
fered with,  the  processes  of  fermentation  and  decomposition  may 
reach  a  very  high  degree. 

The  antiseptic  action  of  the  gastric  juice  was  noticed  more 

^  Miquel,  Centralbl.  f.  allgem.  Gesundheitspflege,  vol.  ii.  p.  403 :  1884, 

2  Bidder  and  Schmidt,  loc.  cit.,  p.  61. 

3  Heidenhain,  Pflüger's  Arch.,  vol.  xix.  p.  153 :    1879. 

■*  The  method  of  obtaining  the  secretion  from  these  glands  will  be  discussed 
later  on. 

'  Dionys  Szabö,  Zeitachr.  f.  phyaiol.  Chem.,  vol.  i.  p.  155 :  1877. 


SALIVA   AND    GASTRIC   JUICE  133 

than  a  hundred  years  ago  by  Spallanzani.^  He  found  that  by 
moistening  meat  with  gastric  juice  he  could  prevent  decomposi- 
tion for  many  days.  But  when,  ceteris  paribus,  water  was  used 
instead  of  gastric  juice,  an  unbearable  putrid  odor  was  speedily 
developed.  A  snake  had  swallowed  a  lizard.  After  sixteen 
days  Spallanzani  opened  the  stomach  ;  the  lizard  was  half  di- 
gested, but  gave  no  odor  of  decomposition.  Spallanzani  even 
observed  that  the  gastric  juice  not  only  prevented  decomposi- 
tion, but  stopped  putrefaction  which  had  already  begun.  He 
found  that  when  decomposing  meat  was  introduced  into  the 
stomachs  of  various  animals,  it  lost  its  putrefactive  character 
after  a  time,  and  particularly  its  putrid  odor. 

A  strong  point  in  favor  of  the  view  that  the  antiseptic  ac- 
tion of  the  gastric  juice  constitutes  its  chief  importance  is  found 
in  the  fact  that,  in  a  whole  series  of  the  lower  animals,  the 
commencement  of  the  alimentary  canal  secretes  a  fluid  very  rich 
in  mineral  acid,  but  containing  no  ferment,  and  having  no 
special  action  on  the  food.  This  important  fact  was  first  no- 
ticed by  the  zoologist  Troschel.^  He  was  making  a  scientific 
journey  with  his  teacher,  Johannes  Müller,  and  whilst  in  Mes- 
sina he  examined  a  large  species  of  mollusc,  which  is  there 
found  in  the  sea,  the  Dolium  galea.  It  so  happened  that  one 
of  these  creatures,  whilst  being  examined,  suddenly  ejected  from 
its  mouth  a  stream  of  clear  fluid,  which  fell  on  the  floor.  The 
latter  was  covered  with  marble,  and  the  fluid  at  once  caused  a 
violent  ebullition  of  carbonic  acid.  Troschel  collected  a  large 
quantity  of  this  secretion  from  a  number  of  these  molluscs. 
The  weight  of  one  of  the  molluscs  amounted  to  from  1  to  2 
kgrms.,  and  the  two  large  glands  which  pour  the  acid  fluid  into 
the  mouth,  and  are  hence  designated  salivary  glands  by  zoolo- 
gists, weigh  together  from  80  to  150  grms.  On  grasping  the 
proboscis  of  the  animal  by  its  trumpet-like  enlarged  end,  the 
secretion  is  ejected,  and  can  be  collected  in  a  vessel.  The 
quantity  was  very  small,  but  amounted  in  one  case  to  fully  6 
loth^  Prussian  weight.  It  was  therefore  easy  to  collect  a 
quantity  sufficient  for  investigation. 

Troschel,  on  his  return  to  Bonn,  made  over  the  whole  of 
the  secretion  to  the  chemist  Boedeker  for  analysis.     It  struck 

^  Spallanzani,  "  Experiences  sur  la  digestion,"  Trad,  par  Senebier,  pp.  95,  97, 
145,  320,  330,  nouvelle  edit. :  Geneve,  1784.  This  work  is  strongly  to  be  recom- 
mended to  young  physiologists,  as  an  example  of  impartial  investigation,  logical 
conclusions,  indomitable  scepticism,  and  the  purest  enjoyment  of  truth  for  its 
own  sake.    The  same  qualities  are  visible  in  all  Spallanzani's  other  works. 

*  Troschel,  Poggendorff's  Annal.,  vol.  xciii.  p.  614 :  1854  ;  or  Joum.  f.  prakt. 
Chem.,  vol.  Ixiii.  p.  170 :  1854. 

^  [A  '  loth '  is  half  an  ounce.] 


134  LECTURE    X 

Boedeker  at  once  that  the  fluid  displayed  no  trace  whatever  of 
putrefaction  or  fermentation,  or  of  mouldiness,  and  that  it  had 
no  smell,  although  it  had  been  kept  for  half  a  year  in  a  stop- 
pered bottle.  The  analysis  yielded  so  large  a  quantity  of  sul- 
phuric acid  that,  after  saturation  of  all  the  bases  present,  pot- 
ash, soda,  magnesia,  a  little  ammonia,  and  a  trace  oiP  lime,  there 
still  remained  2.7  per  cent.  HgSO^.  In  addition,  the  secretion 
contained  0.4  per  cent,  of  hydrochloric  acid.  These  results  of 
Troschel  and  Boedeker  were  confirmed  by  Panceri  and  De 
Luca.^  They  found  in  three  analyses  of  the  saliva  of  Dolium 
galea,  3.3,  3.4,  4.1  per  cent,  of  free  sulphuric  acid.  They  also 
proved  the  presence  of  secretions  containing  free  sulphuric  acid 
in  another  species  of  mollusc. 

In  more  recent  times,  the  saliva  of  Dolium  galea  has  been 
examined  by  Maly.^  He  has  determined  the  sulphuric  acid 
by  titration,  and  found  0.8  and  0.9  per  cent.  HgSO^  in  two 
determinations.  The  secretion  had  no  digestive  influence  on 
any  article  of  food.  Proteid  and  starch  remained  totally  un- 
changed. 

Fr^d^ricq^  found  that  the  salivary  glands  in  the  octopus 
had  an  acid  reaction.  The  extract  of  these  glands  had  no 
digestive  influence. 

We  must  now  ask  how  this  remarkable  phenomenon,  the 
secretion  of  the  strongest  free  mineral  acids  from  the  alkaline 
tissues,  is  to  be  explained. 

That  the  tissue  of  the  gastric  mucous  membrane  does  as  a 
matter  of  fact  give  an  alkaline  reaction,  has  been  shown  by 
Brücke*  by  the  following  experiment.  He  removed  a  strip  of 
the  muscular  coat  from  a  rabbit  recently  killed,  and  then  with 
curved  scissors  cut  out  a  piece  of  the  parenchyma  of  the  glands 
without  quite  touching  the  internal  surface  of  the  mucous  mem- 
brane. The  fragment  thus  obtained  could  be  crushed  between 
blue  litmus  paper  without  causing  a  red  spot,  whilst  this  was 
produced  at  once  on  contact  with  the  internal  surface. 

The  material  for  the  formation  of  the  hydrochloric  acid  in 
the  gastric  glands  is  undoubtedly  yielded  by  the  blood  in  the 
form  of  chlorid  of  sodium,  which  is  the  chief  constituent  of 
the  ash  of  the  blood-plasma  and  of  lymph.  But  nevertheless 
carbonate  of  soda  is  contained  in  both  blood  and  lymph,  which 
have  in  consequence  an  alkaline  reaction.     How  then  is  the 

^  S.  de  Luca  and  P.  Panceri,  Compt.  rend.,  vol.  Ixv.  pp.  577,  712 :  1867. 
'  Maly,  Sitzungsber.  d.  k.  Akad.  d.  Wissensch.     Math.  nat.  Classe,  vol.  Ixxii. 
part  2,  p.  376:  Wien,  1880. 

*  Fredericq,  Bulletins  de  I' Acad.  Roy.  de  Belgique,  ser.  ii.  vol.  xlvi.  No.  11 : 
1878.      .  ' 

*  Brücke,  Sitzungsber.  d.  Wien.  Akad.,  vol.  xxxvii.  p.  131:  1859. 


SALIVA    AND    GASTRIC    JUICE  135 

hydrochloric  acid  set  free  from  the  sodium  chlorid  of  the 
alkaline  plasma  ?  Two  suppositions  alone  are  possible.  Either 
the  hydrochloric  acid  is  separated  from  the  sodium  by  the  aid 
of  some  kinetic  energy,  or  the  hydrochloric  acid  is  driven  from 
its  base  by  another  acid.  With  regard  to  the  first  possibility, 
we  are  only  acquainted  with  one  kind  of  kinetic  energy  which 
is  able,  outside  the  organism,  to  separate  hydrochloric  acid 
from  an  aqueous  solution  of  chlorid  of  sodium,  and  that  is  the 
electric  current.  There  was  a  period  in  the  development  of 
physiology  when  a  tendency  existed  to  ascribe  anything  which 
could  not  be  understood  to  electricity.  It  was  then  thought 
that  the  appearance  of  free  hydrochloric  acid  in  the  gastric  juice 
could  be  explained  by  the  supposition  of  electrical  currents 
in  the  gastric  glands.  But  at  the  present  day  this  view  is 
hardly  entertained ;  neither  are  there  any  valid  grounds  for  its 
adoption. 

With  regard  to  the  second  supposition,  the  displacement 
of  the  hydrochloric  acid  by  another  acid,  there  was  till  recently 
a  prejudice  against  it,  since  it  was  thought  that  an  acid  could 
only  be  displaced  by  a  stronger  acid.  The  question  is  whether 
this  opinion  is  well  founded,  and  what  we  mean  by  the  terms 
weaker  and  stronger  acid.  The  most  plausible  definition  is 
obviously  the  following  :  of  two  acids,  the  one  which  requires 
a  greater  expenditure  of  energy  to  separate  it  from  the  same 
base,  and  which,  on  reuniting,  produces  more  energy,  is  the 
stronger.  In  this  sense,  as  proved  by  calorimetric  experiments, 
sulphuric  acid  is  stronger  than  hydrochloric  acid,  hydrochloric 
acid  than  lactic  acid,  and  the  latter  than  carbonic  acid.  But  it 
is  erroneous  to  suppose  that  the  weaker  acid  is  never  able  to 
drive  out  the  stronger.  From  the  researches  of  Jul.  Tbomsen,^ 
we  know  with  certainty  that  every  acid  drives  out  a  portion 
of  every  other  acid  from  its  union  with  a  base.  It  may  even 
happen  that  the  weaker  acid  unites  with  the  bulk  of  the  bases 
present.  If  hydrochloric  acid  be  added  to  a  solution  of  sul- 
phate of  soda,  heat  is  absorbed,  and  the  temperature  of  the  solu- 
tion falls ;  more  heat  is  used  up  in  the  separation  of  the  soda 
from  the  sulphuric  acid  than  is  produced  by  its  union  with 
hydrochloric  acid.  With  the  aid  of  the  calorimeter,  it  is  pos- 
sible to  follow  these  experiments  quantitatively  with  exactness. 
From  the  known  amount  of  heat  produced  by  the  union  of 
hydrochloric  acid  and  sulphuric  acid  with  sodium,  and  from 
the  diminution  of  temperature  observed  when  hydrochloric  acid 
acts  on  a  solution  of  sulphate  of  sodium,  it  can  be  exactly  calcu- 

^  Jul.  Thomsen,  "  Thermochemische  Untersuchungen,"  Poggendorff's  Annul., 
vols,  cxxxviii.-cxliii.:  1869-1871. 


136  LECTUEE   X 

lated  how  much  sulphuric  acid  is  displaced  by  the  hydrochloric 
acid.  Thomsen  found  that  when  equivalent  quantities  of  hydro- 
chloric acid  and  sulphate  of  soda  react  upon  one  another,  the 
hydrochloric  acid  combines  with  two-thirds  of  the  sodium  pres- 
ent, leaving  only  one-third  to  the  sulphuric  acid.  The  weaker 
acid  takes  up  twice  as  much  as  the  stronger.  Strength,  as  defined 
above,  is  therefore  not  the  determining  factor.  We  are  com- 
pelled to  form  a  new  idea  of  the  different  strengths  of  chemical 
affinity,  and  Thomsen  has  introduced  the  term  "  avidity "  to 
express  this  idea.  The  avidity  of  hydrochloric  acid  is  therefore 
twice  as  great  as  that  of  sulphuric  acid. 

Thomsen  found  the  avidity  of  organic  acids  to  be  much  less. 
The  avidity  of  oxalic  acid  is  four  times  less  than  that  of  hydro- 
chloric acid ;  that  of  tartaric  acid  twenty  times,  that  of  acetic 
acid  thirty-three  times,  less.  If  therefore  equivalent  quantities 
of  acetic  acid,  hydrochloric  acid,  and  soda  react  upon  one 
another  in  an  aqueous  solution,  the  acetic  acid  takes  ^^  of  the 
total  soda ;  the  hydrochloric  H.  If,  however,  more  than  one 
equivalent  of  acetic  acid  react  upon  one  equivalent  of  hydro- 
chloric acid  and  one  equivalent  of  sodium,  more  than  -^^  of 
the  sodium  unites  with  the  acetic  acid,  and  the  further  in- 
crease will  be  in  proportion  to  the  greater  amount  of  acetic 
acid  present.  This  phenomenon  is  known  by  the  name  ot 
the  "  influence  of  mass."  By  the  influence  of  mass,  acids 
of  the  weakest  avidity  are  able  to  unite  with  the  bases  and 
to  displace  acids  of  the  greatest  avidity.  No  acid  has  an 
avidity  =  0.  Even  carbonic  acid,  feeble  as  it  is,  must  be  able, 
by  the  influence  of  mass,  to  displace  a  part  of  the  strongest 
acid. 

Finally,  we  must  suppose  that  even  the  weakest  acid,  water, 
may  displace  a  part  of  the  strongest  from  their  salts.  If  we 
dissolve  neutral  chlorid  of  sodium  in  water,  there  will  be,  in 
addition  to  the  chlorid  of  sodium,  a  small  trace  of  HCl  and 
NaOH  contained  in  the  solution.  In  the  case  of  certain 
metallic  salts,  which  form  basic  salts,  soluble  with  difficulty, 
the  action  of  water  in  displacing  the  strongest  mineral  acids 
can  be  easily  demonstrated.  If  we  dilute  a  solution  of  nitrate 
of  bismuth  with  water,  the  basic  salt  is  precipitated,  and  we  find 
free  nitric  acid  in  solution.  In  this  case  the  mass-influence  of 
the  feeble  acid  is  aided  by  the  affinity  of  the  strong  acid  for 
water. 

The  displacement  of  strong  mineral  acids  by  weak  organic 
acids  may  be  shown  in  other  ways  than  the  thermo-chemical. 
Maly  ^  introduced  into   the  lower  portion  of  a  tall  cylinder 

1  Maly,  Liebig's  Annal.,  vol.  clxxiii.  pp.  250-257:  1874. 


SALIVA   AND   GASTEIC   JUICE  137 

a  solution  o'f  common  salt  and  lactic  acid,  and  carefully  poured 
water  upon  it.  After  a  considerable  time  the  upper  stratum 
was  removed  and  analyzed.  It  was  found  to  contain  more 
chlorin  than  was  sufficient  to  saturate  the  sodium  that  was 
present.  It  follows  that  free  hydrochloric  acid  had  difiiised 
into  the  water. 

If  we  take  these  facts  into  consideration,  there  is  nothing 
peculiar  in  the  separation  of  free  hydrochloric  acid  from  alka- 
line blood.  We  know  that  the  blood  always  contains  free  car- 
bonic acid  which,  by  the  influence  of  mass,  has  the  power  of 
setting  free  a  small  amount  of  hydrochloric  acid  from  the  chlo- 
rid  of  sodium.  The  amount  may  be  almost  imperceptible,  but 
as  soon  as  this  small  quantity  of  free  hydrochloric  acid,  which 
corresponds  to  the  free  carbonic  acid,  diffuses  away,  the  carbonic 
acid,  by  its  mass-influence,  must  again  set  free  another  small 
amount  of  hydrochloric  acid,  and  so  on. 

There  is  thus  nothing  extraordinary  in  the  occurrence  of 
free  hydrochloric  acid.  But  what  is  enigmatical  is  the  power 
epithelial  cells  possess  of  directing  the  hydrochloric  acid,  liber- 
ated from  the  chlorid  of  sodium,  always  in  the  one  direction 
towards  the  excretory  duct  of  the  gastric  glands,  and  the  car- 
bonate of  sodium,  formed  from  the  carbonic  acid,  always  in  the 
opposite  direction,  back  towards  the  lymph  and  blood-vessels. 
But  this  enigma  confronts  us  everywhere  in  living  tissue.  Each 
cell  has  the  power  of  attracting  or  rejecting  different  materials, 
according  to  the  object  they  are  destined  to  fulfil,  and  of  for- 
warding them  in  different  directions.^  It  is  therefore  no  fresh 
problem  that  confronts  us  in  the  attempt  to  explain  the  occur- 
rence of  free  hydrochloric  acid  in  the  gastric  glands,  and,  in 
fact,  "  every  explanation  of  the  phenomena  of  nature  consists  in 
referring  an  apparently  fresh  difficulty  back  to  old  and  well- 
known  problems." 

The  mass-action  of  carbonic  acid  appears  also  to  liberate 
the  mineral  acids  in  the  salivary  glands  of  Dolium  galea. 
De  Luca  and  Panceri  observed  that  a  strong  current  of  gas- 
bubbles  arose  from  the  glands  when  they  were  cut  up  and  im- 
mersed in  water.  The  gas,  being  completely  absorbed  by 
potash,  was  therefore  pure  carbonic  acid.  A  gland  weighing 
75  grms.  produced,  when  covered  with  water,  200  c.cms. 
of  carbonic  acid,  or  nearly  three  times  its  volume.  It  must 
likewise  be  remembered  that  the  surrounding  fluid  retained 
a  considerable  quantity  of  carbonic  acid,  and  that  the  gland 
itself  remained  saturated  with  carbonic  acid.  Thus  at  least  four 
times  its  volume  of  carbonic  acid  was  absorbed  in  the  gland. 

^  Compare  above,  p.  4,  and  below  p.  147,  and  Lecture  XXI. 


138  LECTURE    X 

As  water  at  an  ordinary  temperature  absorbs  from  an  atmos- 
phere of  pure  carbonic  acid  its  equal  volume  of  carbonic  acid, 
we  must  conclude  that  the  carbonic  acid  in  the  glands  was  under 
more  than  fourfold  atmospheric  pressure ;  or  we  must  assume 
that  the  carbonic  acid  was  in  part  loosely  combined.  An  exact 
estimate  of  the  tension  of  carbonic  acid  which  would  prevent 
the  escape  of  the  gas  from  the  gland,  would  help  to  decide  this 
question. 

It  is  quite  possible  that  much  carbonic  acid  is  also  liber- 
ated in  the  epithelial  cells  of  the  gastric  glands,  either  by 
a  fermentative  process  or  by  the  oxidation  of  organic  com- 
pounds. 

At  the  same  time  we  are  not  obliged  to  ascribe  the  dis- 
placement of  the  strong  mineral  acids  to  the  most  feeble  acid, 
carbonic  acid.  It  is  quite  conceivable  that,  in  the  epithelial 
cells  of  the  glands,  organic  acids  may  be  liberated  by  the 
action  of  ferments  from  neutral  organic  compounds  —  for  in- 
stance, lactic  acid  from  neutral  sugar,  which  is  invariably  a 
constituent  of  blood-plasma  and  of  lymph.  It  is  even  possible 
that  the  strongest  mineral  acid,  sulphuric  acid,  may  be  liberated 
by  a  fermentative  action  directly  from  a  neutral  compound  of 
sulphur,  as,  for  instance,  from  proteid.  That  this  is  possible 
may  be  seen  from  an  example  in  organic  chemistry — I  mean 
the  decomposition  of  a  glucoside,  myronic  acid.  The  potassium 
salt  of  myronic  acid,  a  neutral  compound,  splits  up  by  the 
action  of  a  ferment  into  sugar,  oil  of  mustard,  and  bisulphate 
of  potash,  which  latter,  Graham^  has  shown,  at  once  decom- 
poses in  an  aqueous  solution  into  free  sulphuric  acid  and 
neutral  sulphate  of  potash.  Besides  this,  free  sulphuric  acid 
might  also  be  liberated  by  oxidation  from  neutral  organic  sul- 
phur compounds. 

At  present  we  do  not  know  by  which,  of  all  these  con- 
ceivable processes,  the  strong  mineral  acids  are  liberated  in 
glandular  tissue.  I  have  called  attention  to  these  possibilities 
so  as  not  to  be  obliged  to  have  recourse  to  electricity  for  an 
explanation. 

The  secretion  of  the  free  hydrochloric  acid  does  not  occur 
in  all  glands  of  the  gastric  mucous  membrane.  The  mucous 
membrane  in  the  region  of  the  pylorus  which,  even  with  the 
naked  eye,  can  be  distinguished  by  its  pale  color  from  the 
rest  of  the  membrane,  yields  an  alkaline  secretion  which  only 

1  Graham,  Liebig's  Annal.,  vol.  Ixxvii.  p.  80:  1881.  In  a  difiiision  experi- 
ment with  bisulphate  of  potassium,  more  sulphuric  acid  diffused  than  corre- 
sponded to  the  acid  salt,  and  a  little  neutral  sulphate  of  potassium  crystallized  out 
in  the  diffusion-cell. 


SALIVA    AND    GASTRIC    JUICE  139 

contains  pepsin.  The  glands  of  the  rest  of  the  membrane 
yield  an  acid  secretion  which  contains  pepsin  as  well  as  free 
acid.  This  was  shown  to  be  the  case  by  Klemensiewicz  ^  and 
Heidenhain  ^  by  the  following  method  : — 

By  an  incision  in  the  linea  alba  of  a  dog  that  has  been 
fasting  from  thirty-six  to  forty-eight  hours,  the  stomach  is 
drawn  out  by  two  parallel  incisions,  avoiding  the  large  blood- 
vessels, the  pyloric  zone  is  cut  out,  the  two  edges  of  the  re- 
sected stomach  are  sewn  together,  and  the  organ  thus  reduced 
in  size  is  replaced.  Then  the  excised  pylorus  is  sewn  together 
at  one  end  to  form  a  sac,  while  the  other  end  is  sewn  into  the 
abdominal  wound.  By  the  careful  use  of  antiseptics  in  the 
treatment  of  the  wounds,  and  by  abstinence  from  food  during  the 
following  days,  the  animals  are  kept  alive  after  this  severe 
operation.  Heidenhain  was  able  to  observe  one  of  the  dogs, 
that  he  had  experimented  upon,  for  ten  weeks.  The  slimy 
clear  fluid  secreted  in  the  isolated  pylorus  invariably  gave  an 
alkaline  reaction,  and,  on  the  addition  of  0.1  per  cent,  of 
hydrochloric  acid,  produced  a  peptonizing  action  on  proteid. 
As  dilute  hydrochloric  acid  by  itself  cannot  convert  proteid 
into  peptone  at  the  temperature  of  the  body,  we  must  assume 
that  the  pyloric  secretion  contains  a  ferment. 

In  a  similar  method  to  that  adopted  for  the  pylorus, 
Heidenhain  isolated  a  rhombic  portion  of  the  fundus  of  the 
stomach,  converted  it  into  a  sac,  and  attached  the  open  end 
to  the  abdominal  wound.  A  dog  thus  operated  upon  was 
kept  under  observation  for  five  weeks.  The  secretion  collected 
from  the  abdominal  wound  always  possessed  an  acid  reaction, 
and  manifested  a  pronounced  peptonizing  influence,  showing 
that  it  also  contained  pepsin. 

Still  further  progress  has  been  made  in  determining  exactly 
where  the  hydrochloric  acid  arises,  and  special  cells  of  the 
gastric  glands,  the  so-called  border  or  oxyntic  cells,  are  re- 
garded as  its  place  of  origin.  The  reasons  which  are  adduced 
in  favor  of  this  conclusion  are  by  no  means  convincing ;  but 
it  would  lead  me  too  far  to  consider  the  whole  question  in 
detail.' 

Since  it  is  possible  to  keep  an  animal  alive  after  resection 
of  the  pylorus,  the  question  occurs  as  to  whether  the  whole 

^  Rudolf  Klemensiewicz,  Sitzungsberichte  der  Wiener  Akad.,  Math.  nat. 
Classe,  vol.  Ixxi.  part  iii.  p.  249 :  1875. 

2  Heidenhain,  Pflüger's  Arch.,  vol.  xviii.  p.  169:  1878;  and  vol.  xix.  p.  148: 
1879. 

'  An  account  of  the  literature  on  this  question  is  given  in  the  chapter,  "  Phy- 
siologie der  Absonderungsvorgänge,"  by  Heidenhain,  in  Hermann's  "  Handbuch 
der  Physiologie,"  vol.  v.  part  i.:  Leipzig,  1883. 


140  LECTURE    X 

stomach  might  not  be  removed  without  destroying  life.  Such 
an  operation  would  be  likely  to  give  us  much  information  con- 
cerning the  true  importance  of  the  stomach. 

Czerny,  the  eminent  surgeon,  and  his  assistants,  Kaiser 
and  Scriba,  carried  out  this  operation  on  dogs.  In  the  year 
1878,  Kaiser^  published  the  result  of  the  operations,  and  com- 
municated the  facts  that,  of  the  dogs  in  which  the  stomach 
had  been  almost  completely  removed,  one  had  survived  three 
weeks,  another — operated  on  December  22,  1876 — was  still 
living.  At  first  the  animals  were  fed  only  on  very  small 
quantities  of  milk  and  minced  meat,  as  otherwise  vomiting 
ensued.  The  second  dog,  after  a  two-months'  interval,  required 
no  further  care,  and  ate  ordinary  food  like  the  other  dogs. 
The  weight  of  the  dog  before  the  operation  was  5850  grms.; 
after  the  operation  it  fell  to  4490  grms.  by  January  22,  but 
then  increased  again  till  it  amounted  to  7000  grms.  on  Sep- 
tember 10. 

In  Leipzig,  in  the  year  1882,  Ludwig  and  his  pupil  Ogata  ^ 
were  engaged  in  investigating  the  functions  of  the  stomach. 
It  occurred  to  them  that  it  would  be  interesting  to  learn  what 
had  become  of  Czerny's  dogs.  Ludwig  wrote  to  Czerny  at 
Heidelberg,  who  answered  by  sending  the  dog  in  a  perfectly 
healthy  state  to  Leipzig.  It  was  in  excellent  spirits,  and 
ate  all  kinds  of  food  with  a  keen  appetite.  The  feces  were 
normal.  In  consequence  of  the  abundant  food  it  put  on 
weight,  and  it  did  not  appear  to  differ  in  any  way  from  an 
ordinary  dog.  With  Czerny's  consent,  the  dog  was  killed  in  the 
spring  of  1882.  "The  post-mortem  showed  that  only  a  very 
small  portion  of  the  cardiac  end  of  the  stomach  remained,  and 
this  was  dilated  into  a  small  cavity  filled  with  food."  The  dog 
had  therefore  lived  for  more  than  five  years  without  a  stomach. 

Ludwig  and  Ogata  ^  adopted  another  way  of  excluding  the 
stomach  from  participation  in  the  functions  of  digestion,  and 
of  observing  what  variations  from  the  normal  course  of  events 
were  then  produced.  They  introduced  the  food  directly  into 
the  duodenum,  by  means  of  a  fistula  which  had  been  established 
close  to  the  pylorus,  and  then  closed  the  pylorus  by  means  of  a 
gutta-percha  ball  provided  with  a  long  tube  which  projected 
from  the  fistula,  and  by  means  of  which  the  ball  could  be  so 

1  F.  F.  Kaiser,  in  Czerny's  "  Beiträge  zur  operativen  Chirurgie,"  p.  141 : 
1878.  These  results  have  been  confirmed  by  F.  de  Filippi,  Deutsch,  med. 
Wochenschr.,  p.  780:  1894;  J.  Carvallo  and  V.  Paehon,  "  Arch,  de  Physiol.," 

vol.  xxvii.  pp.  349  and  766  :  1896,  and  U.  Monari,  Beitr.  z.  klin.  Chir.,  vol.  xvi. 
p.  479 :  1896. 

2  M,  Ogata,  Du  Bois'  Arch.,  p.  89 :  1883. 
'M.  Ogata,  loc.  cit.,  p.  91. 


SALIVA   AND   GASTRIC    JUICE  141 

filled  with  water   that  the   passage  from  the  stomach  to  the 
duodenum  was  completely  cut  off. 

In  this  way  it  was  possible  to  introduce  at  one  time  very 
large  quantities  of  food,  such  as  pounded  egg  and  minced 
meat,  into  the  duodenum  without  causing  any  disturbance. 
Two  injections  per  diem  were  sufficient  to  maintain  the 
animal's  weight.  The  food  was  almost  completely  used  up, 
and  the  feces  exhibited  normal  characters,  such  as  are  ob- 
served in  feeding  by  the  mouth.  The  only  exception  was  that 
sometimes  the  connective  tissue  of  the  food  was  not  quite  so 
completely  absorbed  as  is  normally  the  case.  It  was  however 
not  a  matter  of  indifference  whether  the  food  was  previously 
cooked  or  not.  For  instance,  minced  meat  was  completely 
absorbed  only  if  given  raw.  If  administered  after  it  had  been 
boiled,  it  was  ejected  per  anum  a  few  hours  later  but  little  or 
entirely  unaltered.  Minced  pork  behaved  in  an  opposite  way, 
and  was  more  completely  digested  after  having  been  lightly 
boiled  than  when  given  raw. 

Ludwig  and  Ogata  conclude  from  their  observations  that 
"  the  stomach  is  not  absolutely  necessary  to  satisfy  the  require- 
ments of  digestion,  either  as  a  reservoir  of  food  or  to  produce 
the  gastric  juice." 

No  experiment  was  made  in  which  a  dog,  after  removal  of 
the  stomach,  was  fed  by  the  direct  introduction  into  the  intes- 
tine of  putrid  meat,  a  diet  which  agrees  very  well  with  normal 
dogs.  The  chief  function  of  the  stomach  would  at  once  have 
been  evident  had  this  been  done. 

Encouraged  by  the  success  of  these  experiments  on  animals 
surgeons  have  carried  out,  with  more  or  less  success,  the  ex- 
tirpation of  the  stomach  in  man,  especially  in  cases  of  cancer  of 
the  stomach.  It  is  advisable,  when  possible,  to  leave  a  portion 
of  the  stomach,  however  small  it  may  be,  since  this  portion  will 
afterwards  increase  in  size,  and  thus  take  on  the  chief  function 
of  the  stomach,  viz.,  as  a  reservoir  and  protective  organ  for  the 
intestine.  In  1895  Professor  Schuchardt,  in  Stettin,  excised 
the  whole  stomach  of  a  patient  with  the  exception  of  a  small 
portion  (about  three  fingers'  breadth)  of  the  cardiac  end.  This 
patient  lived  two  and  a  half  years  after  the  operation,  and  was 
during  this  time  perfectly  well.  At  the  autopsy  a  stomach 
was  found  with  a  capacity  of  500  cc.  It  was  on  this  account 
that  the  patient,  who  at  first  could  take  only  a  small  portion  of 
food  at  a  time,  was  later  on  able  to  take  his  meals  like  any 
other  person.^ 

^  Communicated  by  C.  Schlatter  in  the  Correspondenzbl.  f.  schweizer  Äerzte, 
vol.  xxvii.  p.  705 :  1897.  Here  also  several  other  instances  of  almost  complete 
extirpation  of  the  stomach  are  recorded. 


142  LECTURE   X 

At  the  Congress  of  Swiss  Physicians  in  Olten  on  October  30, 
1897,  the  surgeon,  C,  Schlatter,  of  Zurich,^  showed  a  woman 
in  whom  he  had  completely  extirpated  the  stomach,  on  account 
of  a  hard  tumor  involving  the  whole  stomach  from  pylorus 
to  cardia.  The  esophagus  was  too  far  oif  from  the  duodenum 
to  allow  of  the  two  being  sewn  together.  The  esophagus  was 
therefore  made  to  open  into  a  loop  of  the  small  intestine,  and 
the  upper  end  of  the  duodenum  was  closed  by  sutures.  The 
bile  and  pancreatic  juice  thus  poured  themselves  into  a  blmd 
portion  of  the  gut,  by  which  they  were  conducted  to  the  small 
intestine,  where  the  food  entered  it  through  the  esophagus. 
The  patient  who  had  undergone  this  operation  had  already  sur- 
vived it  eight  weeks  when  she  was  shown  at  the  Meeting,  and 
in  this  time  had  put  on  4.4  kilos,  in  weight.  Of  course  the 
patient  could  take  only  small  quantities  of  fluid  or  of  finely 
minced  food  at  a  time. 

The  antiseptic  powers  of  the  gastric  juice  have,  like  most 
things,  a  limit.  Certain  bacteria  and  among  them  pathogenic 
organisms  exhibit,  especially  in  their  spore  stage,  such  a  resist- 
ance to  chemical  agents  that  the  hydrochloric  acid  of  the 
stomach  does  not  kill  them.  Thus  Falk^  observed  that  the 
tubercle  bacillus  was  not  acted  upon  by  gastric  juice.  An- 
thrax virus,  taken  from  the  spleen  of  animals  which  had  died 
of  splenic  fever,  was  rendered  inert  both  by  gastric  juice  and 
by  a  0.11  per  cent,  solution  of  hydrochloric  acid.  The  spores 
of  anthrax  bacilli  were  as  a  rule  not  affected  by  dilute  hydro- 
chloric acid  or  gastric  juice,  though  they  were  in  a  few  cases. 
These  statements  have  been  fully  confirmed  by  Frank.^ 

The  comma  bacillus,  which  is  said  to  cause  cholera,  is  very 
easily  killed  by  dilute  hydrochloric  acid.  In  consequence,  it  is 
not  possible  to  infect  animals  by  administration  of  the  comma 
bacillus  by  the  mouth.  But  it  is  possible  sometimes  to  excite 
attacks  resembling  cholera,  by  injecting  pure  cultivations  of 
this  bacillus  into  the  small  intestine  or  into  the  stomach,  after 
previously  washing  out  the  organ  with  a  solution  of  carbonate 
of  soda.*  The  bacteria  which  produce  lactic  and  butyric  fer- 
mentations appear  to  be  more  resistant  to  hydrochloric  acid  ; 
at  any  rate,  they  are  found  very  frequently,  probably  always, 
in  the  human  intestine,^  and  after  eating  carbohydrates,  a  small 

^  loc.  cit.  2  Falk,  Virchow's  Arch.,  vol.  xciii.  p.  117 :  1883. 

3  Frank,  Deutsche  med.  Wochensch.,  No.  24:  1884.  Compare  also  H.  Ham- 
burger, "  Ueber  d.  Wirkung  des  Magensates  auf  pathogene  Bacterien,"  Dissert.: 
Breslau,  1890.    A  complete  account  of  the  literature  is  here  given. 

*  Nicati  et  Rietsch,  Eev.  Seien.,  p.  658 :  1884 ;  R.  Koch,  Deutsch,  med. 
Wochensch.,  No.  45  :  1884. 

5  H.  Notlinagel,  Centralbl.f.  d.  med.  Wissensch.,  No.  2  :  1881. 


SALIVA    AND    GASTRIC    JUICE  J  43 

amount  of  lactic  and  butyric  acids  is  probably  always  found  in 
the  stomach.-  It  has  often  been  asserted  that  this  decomposition 
is  produced  by  unorganized  ferments,  but  it  has  never  been 
strictly  proved/  In  the  normal  feces  of  man,  other  species  of 
bacteria  are  constantly  found. ^ 

Recently,  Nencki  and  his  pupils^  have  investigated  the 
microorganisms  occurring  in  the  intestinal  contents  obtained 
from  a  fecal  fistula  affecting  the  lower  end  of  the  small  in- 
testine of  a  patient.  On  meat  diet  they  found  six  different 
kinds  of  bacteria,  one  kind  of  yeast,  and  one  mould.  On 
vegetable  diet  (peas)  there  were  also  yeasts,  but  no  mould. 
There  were  also  six  kinds  of  bacteria,  of  which  only  one  was 
identical  with  those  found  on  a  meat  diet.  These  microorgan- 
isms were  grown  in  pure  cultures  in  order  to  determine  what 
part  each  species  played  in  the  processes  of  decomposition  oc- 
curring in  the  intestine. 

In  pathological  conditions,  as  in  so-called  catarrh  of  the 
stomach,  when  the  secretion  of  free  hydrochloric  acid  is  sup- 
pressed, and  the  amount  of  alkaline  mucus  yielded  by  the  sur- 
face of  the  stomach  is  increased,  the  reaction  may  indeed  become 
alkaline,  and  then  all  sorts  of  bacteria  are  able  to  grow  lux- 
uriantly.* Lactic  and  butyric  acids  especially  are  formed  in 
abundance.  The  presence  of  acetic  acid  has  also  been  demon- 
strated ;  this  is  probably  produced  from  the  alcohol,  owing  to 
the  oxidizing  influence  of  the  air  which  has  been  swallowed. 
Alcohol  arises  by  fermentation  from  the  carbohydrates.  Not 
only  does  yeast,  which  has  actually  been  observed  in  the 
stomach,  produce  alcohol,  but  certain  varieties  of  bacteria  ap- 
pear also  to  do  so.^ 

The  gases  which  are  formed  by  the  processes  of  fermentation 
in  the  stomach  are  carbonic  acid  gas,  hydrogen,  and  marsh  gas.^ 
Under  pathological  conditions  they  may  be  formed  in  consider- 
able quantities,  and  so  cause  dilatation  of  the  organ.  In  one 
case  of  dilatation  of  the  stomach  Fr.  Kuhn^  found  that  one 

1  See  Ferd.  Hueppe,  llittheil.  a.  d.  kaiserl.  Gesundheitsamte.,  vol.  ii.  p.  309  : 
Berlin,  1884.    Nencki  u.  Sieber,  Journ.  f.  prakt.  Chem.,  vol.  xxvi.  p.  40:  1882. 

2  See  Berthold  Bienstock,  Zeitschr.  f.  klin.  Med.,  vol.  viii.  p.  1:  1884;  L. 
Brieger,  Zeitschr.  f.  physiol.  Chem.,  vol.  viii.  p.  306  :  1884. 

ä  Macfadyen,  Nencki,  and  Sieber,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol. 
xxviii.  p.  325:  1891. 

■*  An  account  of  the  microorganisms  which  occur  in  the  stomach  under 
pathological  conditions,  as  well  as  the  literature  of  the  subject  will  be  found  in 
the  paper  by  W.  de  Bary,  "Beitr.  zur  Kenntniss  der  niederen  Organismen  im 
Mageninhalte"  (Arch.  f.  exp.  Path.,  vol.  xx.  p.  243:  1885). 

^  L.  Brieger,  Zeitschr.  f.  physiol.  Chem.,  vol.  viii.  p.  308:  1884. 

«G.  Hoppe-Seyler,  Deutsch.  Arch.  f.  klin.  3fed.,  vol.  1.  p.  82:  1892. 

''  Fr.  Kuhn,  Zeitschr.  f.  klin.  3Ied.,  vol.  xxi.  p.  584 :  1892. 


144  LECTUEE   X 

liter  of  gastric  contents  developed  four  liters  of  gas  in  four 
hours  when  kept  outside  the  body  at  the  body  temperature. 
This  gas  had  the  following  composition  : — 

CO2 20.0  per  cent. 

O 8.3        " 

H 30.9       " 

CH^ 0.3 

N 40.5       " 

CO A  trace 

At  times  sulphuretted  hydrogen  may  also  be  formed  in  the 
stomach  contents.^ 

If  the  organic  acids  reach  the  esophagus,  they  cause  heart- 
burn by  the  irritation  of  the  mucous  membranes  of  the  esopha- 
gus and  fauces.  This  symptom  is  usually  treated  with  car- 
bonate of  soda  or  magnesia,  without  considering  that  the  cause 
of  the  disorder  is  thereby  increased  rather  than  diminished. 
The  free  acids  are  neutralized  by  the  drug,  and  the  growth  of 
the  fungi  and  fermentation  proceed  more  rapidly.  The  only 
proper  treatment  of  heart-burn  would  be  to  recommend  absti- 
nence to  the  patient,  until  the  stomach  was  empty  and  disin- 
fected by  its  normal  hydrochloric  acid. 

The  contents  of  the  stomach  in  a  considerable  number  of 
diseases  have  recently  been  examined  by  means  of  the  stomach- 
pump.^  It  has  been  found  that  the  free  hydrochloric  acid  is 
frequently  absent  in  the  gastric  juice  of  the  patients,  whilst 
pepsin  is  always  present.^  For  this  reason,  dilute  hydrochloric 
acid  is  frequently  prescribed  as  a  remedy  in  dyspepsia.  Many 
practitioners  assert  that  they  have  obtained  a  favorable  result 
with  it.  I  would  however  warn  against  a  too  energetic 
treatment  with  free  hydrochloric  acid,  especially  a  very  pro- 
longed use  in  chronic  gastric  trouble.  Hydrochloric  acid  is 
partly    excreted   in    a   free    state   by   the    kidneys.     We   are 

1  J.  Boas,  Deutsch,  med.  Wochenschr.,  No.  49,  p.  1110 :  1892. 

2  O.  Minkowski,  Mittheilungen  aus  der  med.  Klinik  zu  Königsberg  i.  Pr.,  p.. 
148 :  1888.    The  earlier  literature  is  discussed  here. 

^  It  has  frequently  been  asserted  that  free  hydrochloric  acid  is  partly  or 
completely  replaced  by  lactic  acid,  even  in  the  normal  gastric  juice,  but  espe- 
cially in  certain  diseases.  It  has  even  been  asserted  that  the  absence  of  free 
hydrochloric  acid  might  serve  for  diagnostic  purposes,  its  absence  having  been 
regarded  as  indicative  of  carcinoma  of  the  pylorus.  A  whole  series  of  convenient 
reactions  for  the  demonstration  of  free  hydrochloric  acid  have  also  been  devised. 
But  these  tests  have  not  proved  reliable,  nor  has  the  absence  of  free  hydrochloric 
acid  as  a  sign  of  a  definite  malady  been  found  to  be  trustworthy.  Just  as  little 
has  the  presence  of  lactic  acid  as  a  constituent  of  normal  gastric  juice  been 
proved.  It  would  appear  that  the  lactic  acid  found  in  the  stomach  never  comes 
from  the  gastric  glands,  but  always  from  the  carbohydrates  of  the  food.  An 
account  of  the  extensive  literature  on  this  subject  will  be  found  in  Deutsch.  Arch, 
f.  klin.  Med.,  vol.  xxxix.  p.  233  :  1886,  by  J.  von  Mering  and  A.  Cahn,  entitled 
"  Die  Säuren  des  gesunden  und  kranken  Magens." 


SALIVA    AND    GASTEIC    JUICE  145 

ignorant  whether  we  should  not  be  throwing  too  much  work 
upon  these  organs,  and  whether  we  should  not  injure  their  tis- 
sue by  a  too  prolonged  use  of  it.  We  are  also  unaware  what 
other  tissues  are  affected  by  the  hydrochloric  acid  on  its  way 
from  the  stomach  to  the  kidney,  and  what  variations  from  their 
normal  chemical  processes  it  causes.  A  diminution  of  their 
alkalescence  can  never  be  a  matter  of  indifference,  since  the  in- 
tensity of  the  processes  of  oxidation  and  disintegration  must  be 
intimately  bound  up  with  the  reaction  of  the  tissue,  judging  at 
any  rate  from  analogous  chemical  processes  that  we  are  familiar 
with  outside  the  body.  So  long  as  we  are  ignorant  on  these 
points,  we  must  be  cautious  in  the  use  of  powerful  remedies 
like  free  mineral  acids.  In  most  cases,  the  best  advice  would 
perhaps  be  that  of  abstinence,  until  the  whole  lining  of  the 
stomach  has  become  disinfected  by  normal  undiluted  gastric 
juice.  Even  in  weakened  and  anemic  individuals  abstinence  is 
perhaps  more  effectual  than  hydrochloric  acid  and  pepsin,  ac- 
companied by  more  food  than  their  instinct  tells  them  they  can 
dispose  of.  The  administration  of  preparations  of  pepsin  and 
pancreatin  is  a  useless  measure. 

It  should  also  be  noted  that  to  begin  a  meal  with  soup,  and 
to  drink  much  during  a  meal,  are  not  rational  proceedings ;  be- 
cause the  gastric  juice  becomes  too  much  diluted,  and  loses  its 
disinfectant  properties.  There  is  an  ancient  and  good  dietetic 
rule,  not  to  drink  for  an  hour  or  two  after  eating,  when  thirst 
is  actually  felt.  It  is  noticeable  that  to  the  healthy  instinct  of 
children  soup  is  repugnant.  At  periods  when  cholera  is  preva- 
lent, it  is  advisable  to  avoid  all  voluminous  foods  and  to  reduce 
liquids  to  a  minimum,  so  that  the  whole  contents  of  the  stomach 
may  be  impregnated  with  hydrochloric  acid  of  the  necessary 
concentration. 

The  question  as  to  why  the  stomach  does  not  digest  itself  is 
one  which  has  caused  much  discussion.  The  tissues  of  the 
stomach  consist  entirely  of  digestible  matter — proteid  and  gela- 
tin. In  fact,  as  soon  as  life  ceases,  self-digestion  of  the  stomach 
takes  place.  In  post-mortem  examinations,  it  is  common  to 
find  a  part  of  the  mucous  membrane  of  the  stomach  softened 
or  dissolved,  and  this  phenomenon  is  especially  marked  in  the 
bodies  of  healthy  and  powerful  individuals  who  have  met  with 
a  sudden  death  in  the  midst  of  full  digestion.  The  old  doc- 
trine, that  the  '  softening  of  the  stomach '  was  a  pathological 
process  going  on  during  life,  is  now  definitely  rejected.^  The 
reason  why  the  process  of  digestion  does  not  proceed  further  in 

■^  Elsässer's  "  Die  Magenerweichung  der  Säuglinge  "  (Stuttgart  and  Tübingen, 
1846),  should  be  read  in  this  connection.    The  earlier  literature  is  also  critically 

10 


146  LECTURE   X 

the  dead  body  is  due  to  the  process  of  cooling  down  which 
takes  place. 

If  a  dog  be  killed  during  digestion  and  the  body  be  kept 
warm,  we  find,  after  two  or  three  hours,  not  only  a  self-diges- 
tion of  the  stomach,  but  also  of  the  neighboring  parts,  liver 
and  spleen.  Why  does  this  solution  not  take  place  in  the  liv- 
ing animal  ?  This  question  was  taken  up  by  John  Hunter,^ 
who  supposed  that  "  the  living  principle  "  hindered  self-diges- 
tion. CI.  Bernard  ^  thought  to  refute  this  view  by  the  follow- 
ing experiment.  He  placed  the  leg  of  a  living  frog  into  the 
gastric  fistula  of  a  living  dog.  The  leg  was  soon  digested, 
and  the  frog  remained  alive.  The  living  principle  had  not 
therefore  protected  the  frog.  Pavy^  introduced  the  ear  of  a 
live  rabbit  into  the  gastric  fistula  of  a  dog.  A  large  part  of 
the  ear  was  digested  in  a  few  hours,  the  tip  being  entirely 
dissolved. 

Pavy*  thought  that  an  explanation  of  the  power  of  resist- 
ance possessed  by  the  living  gastric  mucous  membrane  was  to 
be  found  in  the  quantity  of  blood  contained  in  it.  He  sup- 
posed that  the  constant  rapid  rush  of  alkaline  blood  and  alka- 
line lymph  through  the  tissues  did  not  allow  the  pepsin,  which 
can  only  peptonize  in  acid  solution,  to  do  its  work.  If  the 
circulation  were  arrested,  self-digestion  began.  Pavy  showed 
that,  after  tying  the  blood-vessels  of  the  stomach  in  dogs,  a 
part  of  the  mucous  membrane  was  digested ;  in  rabbits,  even 
perforation  of  the  stomach  set  in.  He  opened  a  dog's  stom- 
ach and  ligatured  a  portion  of  the  opposite  wall  so  that  the 
piece  that  was  tied  hung  into  the  stomach,  and  the  piece  was 
digested  as  if  it  had  been  swallowed.  Pavy  concludes  from 
these  experiments  that  the  alkalies  in  the  blood  prevented 
self-digestion ;  and  this  interpretation  has  been  commonly  ac- 
cepted. But  the  conclusion  is  not  correct.  The  alkalies  are 
not  the  only  things  carried  to  the  epithelial  cells  by  the  blood. 

treated  here.  The  most  prominent  pathological  anatomists  and  medical  men 
have  adopted  Elsässer's  view,  that  the  softening  of  ,the  stomach  is  a  post-mortem 
process.  It  is  only  in  very  rare  and  exceptional  instances  that  softening  and 
perforation  of  the  stomach  set  in  before  death.  See  W.  Mayer,  "  Gastromalacia 
ante  mortem,"  Dissert,  inaug.  Erlang :  Leipzig,  1871. 

^  J.  Hunter,  "  On  the  Digestion  of  the  Stomach  after  Death,"  Phil.  Trans.  : 
June  18,  1772;  and  "Observations  on  Certain  Parts  of  the  Animal  Economy  "  : 
London,  1786. 

2  CI.  Bernard,  "  Le5ons  de  physiologic  experim.,"  &c.,  II.  p.  406:  Paris, 
1856. 

'  F.  W.  Pavy,  "  On  the  Gastric  Juice,"  &c.,  Guy's  Hospital  Reports,  vol.  ii. 
p.  265  :  1856. 

*  F.  W.  Pavy,  "  On  the  Immunity  enjoyed  by  the  Stomach  from  being  digested 
by  its  own  Secretion  during  Life,"  Phil.  Trans.,  vol.  cliii.  part.  i.  p.  161 :  1863 ; 
and  "  On  Gastric  Erosion,"  Guy's  Hospital  Reports,  vol.  xiii.  p.  494  :  1868. 


SALIVA   AND   GASTßlC   JUICE  147 

The  blood  brings  to  the  glandular  cells  everything  which  is 
necessary  to  fulfil  their  functions.  If  the  supply  of  blood  be 
cut  off,  those  vital  functions  which  resist  the  action  of  the 
pepsin  ferment  must  also  cease.  Why  does  not  the  pancreas 
digest  itself,  as  pancreatic  ferment  is  effective  in  a  neutral  and 
alkaline  solution? 

Here  we  are  face  to  face  with  an  unsolved  problem.  But  it 
is  not  a  new  one ;  as  the  epithelial  cells  of  the  gastric  glands 
liberate  free  hydrochloric  acid  and  still  remain  alkaline,  so  the 
epithelial  cells  of  the  pancreatic  gland  secrete  the  ferment  and 
themselves  remain  free  from  ferment.  We  see  the  same  thing 
going  on  in  every  vegetable  cell.  The  cell  sap  which  fills  up 
cavities  in  the  protoplasm  of  the  cell  is  acid,  the  cell  itself, 
like  all  contractile  protoplasm,  is  alkaline.  The  cell  sap  is 
frequently  brilliantly  colored,  while  the  cell  itself,  which 
produces  the  coloring  matter,  is  colorless.  But  as  soon  as 
life  ceases,  as  soon  as  the  vital  phenomena,  the  visible  ameboid 
movements,  stop,  the  incomprehensible  power  of  selecting 
substances  likewise  disappears ;  the  laws  of  diffusion  are  in  no 
way  interfered  with,  and  the  protoplasm  becomes  tinged  with 
coloring  matter.  This  inexplicable  power  of  separating  and 
distributing  the  substances  according  to  the  object  in  view 
is  possessed  by  every  cell  in  our  bodies  (compare  above,  p. 
137). 

Pavy  relies  upon  the  fact  that  self-digestion  occurred  after 
the  introduction  of  large  quantities  of  acid  into  the  stomach, 
even  when  the  circulation  was  not  disturbed,  to  prove  his  view 
that  circulating  blood  prevents  self  -  digestion  only  by  its 
alkalinity.  In  this  case,  Pavy  considers  the  alkalies  do  not 
sujffice  to  prevent  the  action  of  the  acids.  He  injected  3  ozs. 
(=  93  grms.)  of  dilute  hydrochloric  acid,  which  contained  3 
drms.  (=  12  grms.)  HCl,  into  the  stomach  of  a  dog,  and  at  the 
same  time  tied  the  pylorus  and  the  esophagus,  avoiding  the 
vessels.  The  dog  died  in  an  hour  and  forty  minutes,  and  the 
post-mortem,  which  was  immediately  made,  showed  solution  of 
the  gastric  mucous  membrane,  and  perforation  of  the  wall  of  the 
stomach  at  the  cardiac  orifice.  But  this  experiment  does  not 
justify  any  conclusion.  The  amount  of  hydrochloric  acid  in- 
jected was  much  too  large.  Pavy  might  have  destroyed  the 
wall  of  the  stomach  equally  well  with  caustic  potash. 

It  has  often  been  attempted  to  refer  the  origin  of  the  round 
gastric  ulcer  to  self-digestion.  But  the  danger  of  self-digestion 
is  by  no  means  so  great  as  was  formerly  believed.  It  has  been 
shown,  by  numerous  researches,  that  the  wall  of  the  stomach 
has  a  decided  tendency  to    heal   rapidly  after  wounds  of  the 


148  LECTURE    X 

most  varied  description.  This  is  conclusively  proved  by  the 
favorable  results  of  operations  on  the  stomach  in  animals  and 
human  beings.  The  most  plausible  hypothesis  on  the  cause 
of  the  gastric  ulcer  has  been  advanced  by  Virchow/  who  con- 
siders that  some  kind  of  disturbance  in  the  circulation  is  at  the 
root  of  the  disease.  And,  in  fact,  Panum  ^  succeeded  in  pro- 
ducing hemorrhagic  infarctions  with  the  subsequent  formation 
of  ulcers  in  dogs,  by  embolic  plugging  of  the  smallest  arteries 
of  the  gastric  mucous  membrane.  These  results  are  quite 
in  harmony  with  Pavy's  above-mentioned  experiments.  But 
it  has  very  rarely  been  found  that  thrombotic  or  embolic 
plugging  precedes  the  round  gastric  ulcer  in  human  beings.  It 
has  therefore  been  assumed  that  the  round  gastric  ulcer 
was  caused  by  abnormal  increase  of  acid  in  the  gastric  juice, 
or  in  the  contents  of  the  stomach.  But  this  supposition  is 
utterly  unsupported  by  fact.  It  is  also  to  be  noted  that  the 
gastric  ulcer  is  generally  situated  in  the  pylorus  and  in  the 
small  curvature,  very  seldom  in  the  fundus,  where  the  acidity 
is  greatest.  The  etiology  of  the  Ulcus  ventriculi  is  still  in- 
volved in  obscurity. 

I  must  not  omit  to  mention  that  one  of  the  functions  of  the 
stomach  consists  in  the  absorption  of  nutritive  substances. 
The  process  undoubtedly  commences  in  this  section  of  the  diges- 
tive tract.  The  most  recent  and  careful  researches  on  this  func- 
tion we  owe  to  J.  von  Mering  ^  and  his  pupils.  Mering  established 
duodenal  fistulse  in  dogs  and  then  introduced  water  or  solutions 
of  food-stuifs  into  their  stomachs.  When  pure  water  was  given, 
it  flowed  out  of  the  fistula  even  while  the  animals  were  drink- 
ing, but  always  in  spurts.  If  the  finger  were  introduced  into 
the  pylorus,  this  intermittent  flow  was  found  to  be  due  to 
the  alternate  contraction  and  relaxation  of  the  pyloric  orifice. 
Each  minute  the  pylorus  opened  two  to  six  times,  each  time  letting 
out  from  2—15  cc.  of  water.  In  over  100  experiments,  in  which 
a  measured  quantity  of  water  was  given  by  the  mouth,  almost  the 
exact  amount  was  recovered  from  the  duodenal  fistula,  and 
indeed,  on  one  or  two  occasions,  a  few  cc.  over  and  above. 
Thus  in  one  large  dog,  after  440  cc.  water  had  been  taken  by 
the  mouth,  445  cc.  flowed  out  from  the  fistula  within  the  next 


*  Virchow  in  his  Arch.,  vol.  v.  p.  281 :  1853. 

2  Panum,  Virchow's  Arch.,  vol,  xxv. :  1862. 

3  J.  von   Mering,  assisted  by   Dr.    Aldehoff  and   Dr.   Happel,  "  Ueb.   die 
Function  des  Magens."    Separatabdruck  a.  d.  Verhandlungen  des  III.  Congresses 

f.  innere  Med.  zu  Wiesbaden,  1893.  For  the  older  work  see  H.  Tappeiner, 
"  lieber  Resorption  im  Magen,"  Zeitschr.  f.  Biolog.,  vol.  xvi.  pp.  497-507 :  1880  ; 
B.  von  Anrep,  "Die  Aufsaugung  im  Magen  des  Hundes,"  Du  Bois'  Arch.,  pp. 
504-514  :  1881 ;  R.  Meade  Smith,  ibid.,  p.  481 :  1884  (experiments  on  frogs). 


SALIVA    AND    GASTRIC    JUICE  149 

thirty  minutes.  Mering  concludes  from  his  experiments  that 
practically  no  water  is  absorbed  from  the  stomach. 

An  obvious  criticism  of  these  experiments  is  that  no  account 
has  been  taken  of  the  salivary  secretion.  A  large  dog  secretes 
in  one  hour  from  30—90  ccm.  of  saliva/  which  gets  into  the 
stomach.  If,  therefore,  only  just  so  much  water  is  recovered 
from  a  duodenal  fistula  as  has  been  taken  by  the  mouth,  we 
must  conclude  that  the  stomach  has  absorbed  an  amount  of 
water  equal  to  the  volume  of  saliva  secreted  during  this  time. 
It  is  to  be  hoped  that  these  experiments  will  be  repeated  in 
combination  with  extirpation  of  the  salivary  glands  or  ligature 
of  their  ducts,  or  that  the  saliva  be  prevented  in  some  other 
way  from  reaching  the  stomach.  It  must  be  further  objected 
that  the  stomach  behaves  quite  differently  when  the  fluid  is 
allowed  to  flow  into  the  intestines  instead  of  escaping  by  the 
duodenal  fistula.  Thus  Mering  states  that  "  if  the  duodenal 
fistula  be  closed  so  that  the  contents  of  the  stomach  can  only 
be  discharged  into  the  intestine,  all  escape  from  the  body  being 
prevented,  a  very  much  longer  time  elapses  before  the  ingested 
water  leaves  the  stomach.  Whereas,  in  a  dog  with  open  fistula 
500  cc.  left  the  stomach  in  less  than  thirty  minutes,  after  closure 
of  the  fistula  in  the  same  dog  a  considerable  amount  of  fluid  was 
still  found  in  the  stomach  sixty  minutes  after  its  introduction. 
If  250  cc.  of  warm  milk  be  introduced  by  means  of  the  fistu- 
lous opening  into  the  duodenum  in  the  course  of  fifteen  minutes, 
and  then  500  cc.  water  be  injected  into  the  empty  stomach,  only 
a  few  cc.  of  fluid  will  leave  the  stomach  within  the  next  half 
hour ;  although  when  the  intestine  is  empty  the  stomach  would 
get  rid  of  the  500  cc.  by  means  of  the  fistulous  opening  in  less 
than  thirty  minutes.  This  arrangement  evidently  indicates  that 
distention  of  the  small  intestine  reflexly  inhibits  the  evacuation 
of  the  stomach." 

If  the  evacuation  of  the  stomach  is  thus  slowed  under  normal 
conditions  by  this  reflex  mechanism,  we  must  grant  the  possi- 
bility that  there  may  be  a  considerable  absorption  of  water  from 
the  stomach. 

In  the  animals  with  a  duodenal  fistula,  the  absorption  of 
water  on  the  other  hand  seemed  to  be  extremely  slight,  as  was 
evident  from  the  fact  that  "they  were  continually  tormented 
with  thirst.  They  drank  water  by  the  liter,  without  assuaging 
their  thirst ;  in  fact,  the  more  they  drank,  the  worse  grew  the 
thirst,  because  a  small  excess  of  fluid  was  secreted  by  the  stomach 
and  lost  to  the  body  with  the  ingested  fluids." 

^  Bidder  and  Schmidt,  "Die  Verdauungssäfte  u.  der  Stoffwechsel."  Mitau 
and  Leipzig,  pp.  12  and  13  :  1852. 


150  LECTURE    X 

If  solutions  of  food-stuffs — grape-sugar,  maltose,  cane-sugar, 
milk-sugar,  dextrin,  or  peptone — were  injected  into  the  stomach 
of  such  animals,  a  portion  of  these  substances  could  not  be  recov- 
ered from  the  fluid  flowing  out  by  the  fistula.  Thus  20  per 
cent,  of  the  dextrose  and  60  per  cent,  of  the  peptones  disap- 
peared. When  30  grms.  of  sodium  chlorid  in  400  cc.  water 
were  introduced,  6.5  grms.  of  the  salt  were  absorbed  in  the 
stomach.  The  fluid  however  increased  in  amount,  so  that  787 
cc.  of  fluid  were  collected  from  the  fistula.  Dilute  solutions  of 
alcohol  behaved  like  the  salt  solution  :  a  portion  of  the  alcohol 
disappeared,  but  the  total  volume  of  fluid  was  largely  increased. 

The  following  experiment  served  also  to  show  that  an  excre- 
tion of  water  proceeds,  pajn,  passu,  with  the  absorption  of  dis- 
solved substances  in  the  stomach.  A  dog  weighing  7  kilos,  was 
morphinized  and  its  pylorus  ligatured.  100  cc.  of  a  66  per 
cent,  solution  of  dextrose  were  then  injected  into  the  empty 
stomach  and  the  esophagus  ligatured.  After  nine  hours  the 
stomach  was  found  to  contain  400  cc.  of  fluid,  with  9  per  cent, 
of  sugar. 

These  interesting  experiments  of  Mering's  are  extremely 
suggestive,  especially  in  their  bearing  on  the  symptomatology 
and  therapeutics  of  pyloric  stenosis  and  dilatation  of  the  stomach. 
For  the  many  new  points  of  view  put  forward  by  this  author, 
I  must  refer  my  readers  to  the  study  of  the  original. 


LECTURE   XI 

THE    PROCESSES    OF    DIGESTION  IN  THE  INTESTINE THE  PAN- 
CREATIC   JUICE    AND    ITS    FERMENTATIVE    ACTION FER- 
MENTS   IN    GENERAL THE    ACTION    OF    THE    PAN- 
CREATIC   JUICE    ON    THE    CARBOHYDRATES^ 

FATS,  AND  PROTEIDS THE  NATURE 

AND  SIGNIFICANCE  OF  PEPTONES 

The  time  during  which  different  articles  of  diet  remain  in 
the  stomach  of  human  beings  varies  very  greatly.  It  does  not 
depend  only  on  the  quality  of  the  food ;  it  also  increases  with 
the  quantity.  The  mechanical  condition,  the  degree  to  which 
it  has  been  masticated,  likewise  affects  it,  as  also  the  intensity 
of  the  preceding  hunger,  and  especially  the  state  of  the  stomach 
at  that  moment,  a  state  which  depends  on  many  physical  and 
psychical  influences.  Numerous  observations  on  people  with 
gastric  fistulse  ^  have  shown  that  the  food  remains  in  a  healthy 
stomach  from  three  to  ten  hours.  In  disease  the  time  is  often 
much  longer,  as  modern  experience  has  discovered  by  means  of 
the  stomach-pump.  The  emptying  of  the  stomach  goes  on  very 
gradually  in  small  portions  at  a  time.  Busch  ^  observed  this  in 
a  woman,  who,  in  consequence  of  a  wound  made  by  a  bull's 
horns,  had  an  artificial  anus  a  little  below  the  duodenum,  from 
which  the  contents  of  the  stomach  oozed  out,  as  they  were  un- 
able to  reach  the  other  opening  of  the  small  intestine.  The 
first  portions  of  food  appeared  in  the  fistulous  opening  as  early 
as  from  fifteen  to  thirty  minutes  after  being  swallowed. 

Three  new  secretions,  all  of  which  yield  an  alkaline  re- 
action, act  immediately  upon  the  food  when  it  reaches  the  in- 
testine ;  they  are  the  pancreatic  juice,  the  intestinal  juice,  and 

^  W.  Beaumont,  "Experiments  and  Observations  on  the  Gastric  Juice,  and 
the  Physiology  of  Digestion,"  reprinted  from  Plattsburgh  edition,  by  Andrew 
Combe,  Edinburgh,  1838;  O.  von  Griinewaldt,  "  Succi  gastrici  humani  indoles 
physic,  et  ehem.,"  &c..  Dissert.:  Dorpati,  1853;  Ann.  Chem.  Pharm.,  vol.  xcii. 
p.  42:  1854;  E.  v.  Schröder,  "Succi  gastrici  humani  vis  digestiva,"  Dissert.: 
Dorpati,  1853;  F.  Kretschy,  Deutsch.  Arch.  f.  klin.  Med.,  vol.  xviii.  p.  527: 
1876;  Jul.  Uffelmann,  Arch.  f.  klin.  Med.,  vol.  xx.  p.  535  :  1877. 

^  W.  Busch,  Arch.  /.  path.  Anat.  u.  Physiol.,  vol.  xiv.  p.  140 :  1858. 

151 


152  LECTUEE    XI 

the  bile.  By  their  means,  the  chyme,  which  is  the  name  given 
to  the  acid  contents  of  the  stomach,  is  gradually  neutralized, 
and  usually  presents  in  the  lower  part  of  the  intestine  a  reaction 
which  may  be  only  slightly  acid  or  even  occasionally  alkaline/ 
We  will  first  consider  the  action  of  the  pancreas. 

The  PANCREAS  is  the  digestive  gland  par  excellence.  Its 
secretion,  so  far  as  we  know,  has  no  other  action  than  a 
digestive  one ;  it  effects  chemical  changes  in  all  classes  of 
food,  and  prepares  them  for  absorption.  The  proteids  are  pep- 
tonized, starch  is  split  up  into  soluble  carbohydrates,  the  fats 
into  glycerin  and  fatty  acids.  There  is  scarcely  any  animal 
which  does  not  possess  a  secretion  with  an  action  analogous  to 
that  of  the  pancreatic  juice,  whereas  a  gastric  digestion  is  want- 
ing in  many  vertebrates,  e.  g.,  many  fishes  and  even  the  lowest 
mammals,  echidna  and  ornithorynchus.^  The  invertebrates 
have  neither  a  peptic  digestion  nor  have  they  bile.  But  a 
process  analogous  to  pancreatic  action  has  been  found  wherever 
it  has  been  sought.^  It  can  even  be  recognized  in  the  lowest 
organisms,  the  bacteria  :  a  fluid  containing  bacteria  acts  on  the 
three  main  classes  of  foods  just  like  the  pancreatic  juice.  The 
pancreatic  ferments  have  been  found  absent  only  in  a  few  in- 
testinal parasites.*  This  is  perfectly  clear  for  teleological 
reasons :  the  organisms  are  always  floating  about  in  food  that 
has  been  already  digested. 

Before  proceeding  to  consider  the  modes  of  action  of  the 
pancreatic  juice  in  mammals  and  in  human  beings,  together 
with  the  chemical  changes  which  it  causes  in  the  three  groups 
of  food-stuffs  by  its  ferments,  we  will  first  state  clearly  what  is 
known  concerning  the  nature  and  character  of  ferments.  We 
have  already  made  use  of  the  term  '  ferment '  on  several  occasions. 
It  is  therefore  desirable  that  we  should  now  consider  what  con- 
ception we  are  to  attach  to  this  word. 

■^  On  the  reaction  of  the  intestinal  contents  see  A.  Macfadyen,  M.  Nencki, 
and  N.  Sieber,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxviii.  p.  319 :  1891.  The 
earlier  literature  will  be  found  here.  Compare  also  Schmidt-Mülheim,  Du  Bois' 
Arch.,  p.  56  :  1879 ;  and  Gley  and  Lambling,  Revue  biol.  du  Nord  de  la  France, 
vol.  i. :  1888.  [Vaughan  Harley,  Journ.  Physiol.,  vol.  xviii.  p.  2 :  1895  ;  Moore 
and  Rockwood,  ibid.,  vol.  xxi.  p.  58  :  1897.] 

2  A.  Oppel,  Biol.  Centralbl.,  vol.  xvi.  p.  406:  1896. 

^  Hoppe-Seyler,  "  Ueber  Unterschiede  im  chemischen  Bau  und  der  Ver- 
dauung höherer  und  niederer  Thiere,"  Pflüger's  Arch.,  vol.  xiv.  p.  395 :  1877. 
Compare  also  the  numerous  and  comprehensive  works  on  this  subject  by  F. 
Plateau  in  the  years  1874-1877,  and  the  works  of  Fred^ricq  and  Krukenberg  of 
the  same  time.  An  account  of  the  literature  on  tlie  digestion  of  the  lower 
animals  has  been  given  by  Krukenberg,  "  Vergleichend  physiologische  Vorträge," 
II.;  "Grundzüge  einer  vergleichenden  Physiologie  der  Verdauung  ":  Heidel- 
berg, 1882. 

*  L.  Fredericq,  Bulletins  de  l'Acad.  Roy.  de  Belgique,  ser.  2,  t.  xlvi.  No.  8  : 
1878. 


DIGESTION    IN    THE    INTESTINE  153 

We  will  first  restrict  ourselves  to  facts  derived  from 
observation.  Probably  no  one  has  ever  seen  ferments.  What 
can  be  seen  and  observed  is  merely  the  process  of  which  the 
hypothetical  ferment  is  the  exciting  cause.  This  process  con- 
sists, in  all  cases,  in  the  fact  that  a  complex  compound  splits 
up  into  more  simple  ones,  while  kinetic  energy  in  the  shape  of 
heat  is  set  free.  Therefore  in  all  these  processes  potential 
energy  is  converted  into  kinetic  energy.  The  atoms  pass  from 
an  unstable  into  a  stable  arrangement.  Stronger  affinities  are 
hereby  satisfied.  To  adopt  the  terminology  already  defined 
(pp.  34—35),  the  ultimate  cause  is  the  potential  energy  stored  up 
in  the  complex  molecule,  the  effect  is  kinetic  energy,  and  then 
we  have  to  seek  the  'exciting  cause,'  the  'impetus,'  the 
'liberating  force.'  These  are  termed  ferments  in  some  cases, 
but  not  in  all.  What  therefore  have  the  liberating  forces  in  all 
these  various  processes  in  common,  and  what  distinguishes 
them  from  each  other?  This  can  be  clearly  shown  by  a  series 
of  examples. 

Glyceryl  trinitrate,  so-called  nitroglycerin,  splits  up  into 
carbonic  acid,  water,  nitrogen,  and  oxygen  : — 

2[C3H5(ON02)3]  =  6C0,  +  5HjO  +  6N  +  O. 

A  very  considerable  amount  of  heat  is  developed.  A  highly 
unstable  atomic  arrangement  is  converted  into  a  stable  one. 
The  oxygen,  which  has  a  very  slight  affinity  for  nitrogen  but 
a  very  close  affinity  for  carbon  and  hydrogen,  was  in  the 
original  molecule  combined  with  nitrogen,  but  in  the  smaller 
molecules  resulting  from  the  decomposition,  is  united  with 
carbon  and  hydrogen.  The  impetus  is  given  by  mechanical 
means  such  as  a  knock  or  a  blow,  therefore  by  motion,  or  by 
heat  such  as  a  flame,  another  form  of  motion.  Nitrogen 
trichlorid  splits  up  explosively  with  great  development  of 
light  and  heat  into  nitrogen  and  chlorin  : — 

NCI3  +  NCI3  =  N,  +  Ck  +  CI,  +  C\,. 

Here  again  the  unstable  atomic  arrangement  is  converted  into 
a  stable  one.  Stronger  affinities  are  satisfied.  For  many 
reasons  we  are  compelled  to  adopt  the  conclusion  that  the 
elements,  in  an  uncombined  state,  do  not  consist  of  single 
isolated  atoms,  but  are  united  into  molecules.  The  affinity  of 
nitrogen  atoms  to  each  other,  and  of  chlorin  atoms  to  each 
other,  is  obviously  stronger  than  the  affinity  of  chlorin  atoms 
to  nitrogen  atoms.  The  impetus  to  the  rearrangement  of  the 
atoms  is  given  by  some  mechanical  means  or  by  a  rise  of 
temperature.      lodid  of  nitrogen,  the   formation  of   which  is 


154  LECTÜKE    XI 

analogous  to  that  of  nitrogen  trichlorid,  explodes  even  more 
readily,  if  acted  upon  by  certain  periodic  movements,  wave- 
motions  of  a  definite  velocity  and  wave-length.  It  may  be 
shown  that  it  does  not  explode  on  a  low-toned,  but  that  it 
does  so  on  a  high-toned  plate  or  string.  This  phenomenon  is 
evidently  analogous  to  the  resonance  of  certain  elastic  bodies 
when  struck  by  waves  which  proceed  from  another  sounding 
body.  This  resonance  occurs  as  is  well  known  only  with  notes 
of  a  definite  pitch.  So  that  we  may  also  imagine  that,  if  the 
vibrations  which  act  upon  an  unstable  molecule  have  a  definite 
wave-length,  the  atoms  of  this  molecule  are  thrown  into  corre- 
sponding vibration,  and  this  suffices  to  overcome  the  slight 
attraction  of  the  atoms  to  one  another,  and  thus  to  produce  a 
conversion  into  more  stable  compounds. 

The  explosion  of  the  nitrogen  trichlorid  can  also  be 
brought  about  by  contact  with  various  substances,  such  as 
phosphorus,  phosphorus  compounds  free  from  oxygen,  selenium, 
arsenic,  some  resins  (other  kinds  being  inert),  non-volatile  oils, 
&c.  Here  too  we  might  imagine  that,  from  the  various  mole- 
cular vibrations  of  these  substances  (which  we  call  heat),  we 
get  a  certain  resultant  vibration  which  coincides  in  wave- 
length with  that  of  one  of  the  constituents  of  the  nitrogen  tri- 
chlorid molecule,  and  so  occasions  its  decomposition. 

Potassium  chlorate  splits  up  into  potassium  chlorid  and 
oxygen.  The  dissociation  is  set  up  by  the  application  of  heat. 
But  the  rise  of  temperature  need  not  be  nearly  so  high  when 
certain  substances  are  present,  such  as  peroxid  of  manganese, 
ferric  oxid,  or  cupric  oxid.  The  presence  of  these  substances 
probably  so  modifies  the  heat-waves,  that  the  atoms  of  the 
potassium  chlorate  are  more  easily  thrown  into  responsive 
vibrations,  and  thus  decomposed. 

Peroxid  of  hydrogen  decomposes  on  contact  with  platinum, 
gold,  silver,  peroxid  of  manganese,  &c.  In  these  cases 
it  is  called  an  effisct  of  contact,  or  a  katalytic  effect.  We 
can  form  the  following  hypothesis  of  the  process  which  goes  on 
here,  as  in  the  cases  above  cited  :  the  substance  which  acts 
'  katalytically '  exercises  an  attraction  on  one  of  the  atoms  in 
the  unstable  molecule.  It  does  not  unite  with  the  atom,  but 
the  unstable  arrangement  of  the  atoms  in  the  molecule  is 
altered  to  a  stable  one. 

Grape-sugar  splits  up  into  alcohol  and  carbonic  acid  : — 

CeHiA  =  2C02  +  2CÄO. 

This  change  can  be  shown  to  be  accompanied  by  a  rise  of  tem- 
perature.    This  is  in  accordance  with  the  fact  that  the  heat 


DIGESTION    IN    THE    INTESTINE  155 

of  combustion  of  alcohol  is  less  than  that  of  the  grape-sugar 
from  which  the  alcohol  arose.  Thus  a  part  of  the  potential 
energy  stored  up  in  the  sugar  is  converted  through  decomposi- 
tion into  kinetic  energy,  into  heat.  The  atoms  of  the  sugar 
have  passed  from  a  less  stable  into  a  more  stable  arrangement. 
Stronger  affinities  have  been  satisfied.  The  nature  of  the 
liberating  force  is  in  this  case  still  unknown.  It  is  known 
however  that  the  conversion  takes  place  only  if  two  conditions 
are  fulfilled  :  they  are,  first,  the  presence  of  yeast-cells ;  and 
secondly,  a  certain  temperature — from  10°  to  40°  C.  Judging 
from  analogy  of  the  examples  already  given,  we  should  suppose 
that  here  again  a  form  of  motion  starts  the  decomposition. 
The  motion  might  proceed  from  the  vital  functions  of  the  cell. 
But  it  is  likewise  conceivable  that  certain  substances  are  pro- 
duced in  the  metabolism  of  the  cell,  and  that  these  substances 
act  in  a  similar  manner  to  the  katalytic  bodies  in  the  ex- 
amples adduced  above.  The  yeast-cells  are  called  a  '  ferment.' 
Quite  recently  Ed.  Büchner  ^  has  shown  that  the  presence  of 
living  cells  is  not  necessary  in  order  that  fermentation  may 
take  place.  He  finely  powdered  the  cells  with  quartz  sand, 
treated  them  with  a  little  water,  and  then  subjected  them  in  an 
hydraulic  press  to  a  pressure  of  500  atmospheres.  He  obtained 
in  this  way  an  almost  clear  yellow  fluid  which,  on  mixture  with 
a  solution  of  cane-,  grape-,  fruit-,  or  malt-sugar,  set  up  fermen- 
tation within  half  an  hour.  When  the  mixtures  were  kept  in 
the  ice-chest,  the  fermentation  lasted  a  fortnight.  It  might  be 
thought  that  the  expressed  protoplasm  still  possessed  some 
vital  properties,  especially  as  it  has  often  been  found  that  frag- 
ments of  protoplasm  may  still  present  certain  signs  of  vital 
activity,  such  as  contraction.  In  reply  to  this  objection  may  be 
set  the  fact  observed  by  Büchner  that  the  fermentative  action 
of  yeast-juice  is  not  abolished  by  the  addition  of  chloroform, 
which,  as  is  well  known,  inhibits  all  the  vital  functions  with 
which  we  are  acquainted. 

Cane-sugar  splits  up  into  equivalent  quantities  of  dextrose 
and  levulose.  Here  again  there  is  a  development  of  heat,^  and 
again  the  yeast  plays  a  part.  But  in  this  case  also  it  is  not 
requisite  that  the  cells  should  be  living;  an  aqueous  extract 
from  the  yeast-cells,  killed  with  ether,  is  all  that  is  necessary. 
We  may  assume  that  the  atoms  composing  any  of  the  molecules 
in  this  extract  are  in  a  state  of  oscillation,  or  that  different 
molecules  oscillate  against  each  other,  and  that  the  resultant  of 

^  Ed.  Büchner,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  xxx.  p.  117  :  1897.     Compare 
J.  de  Rey-Pailhade,  Compt.  rend.,  vol.  cxviii.  p.  201 :  1894, 
2  A.  Kunkel,  Pfliiger's  Arch.,  vol.  xx.  p.  509  :  1879. 


156  LECTURE    XI 

these  motions  causes  the  dissociation  of  the  molecules  of  cane- 
sugar.  A  theory  has  been  advanced,  but  not  yet  verified,  that 
the  presence  of  one  particular  chemical  individual  in  the  yeast- 
extract  is  essential  for  the  initiation  of  decomposition.  This  fer- 
ment has  been  termed  invertin.^  An  account  of  the  attempts 
which  have  been  made  to  isolate  the  ferments  will  be  given  later. 

Starch-flour  decomposes  on  boiling  with  dilute  acid  into 
molecules  of  grape-sugar.  In  this  reaction  the  direct  proof 
that  heat  is  produced  cannot  be  given.  But  we  must  assume 
that  this  is  the  case,  because  the  heat  of  combustion  of  the 
grape-sugar  is  less  than  that  of  the  starch.  The  impetus  to 
the  change  may  be  a  special  modification  of  the  increased  molec- 
ular movement  due  to  the  heat  in  presence  of  the  acid ;  or 
we  must  suppose  that  the  acid  attracts  the  sugar  molecules  con- 
tained in  the  starch  molecule,  and  possibly  forms  a  temporary 
compound  which  again  rapidly  breaks  up  with  absorption  of 
water.  The  conversion  of  starch  into  sugar  is  always  accom- 
panied by  hydration,  which  is  the  case  in  the  decomposition  of 
cane-sugar,  and  probably  in  all  similar  decompositions.  I  shall 
return  to  this  point  again. 

Starch-flour  also  splits  up  at  a  moderate  temperature 
into  maltose  and  dextrin,  if  it  comes  into  contact  with  certain 
substances,  which  are  contained  in  germinating  barley  or  in 
saliva  and  in  pancreatic  juice.  But  in  this  case  the  term 
ferments  is  used  as  indicating  chemical  individuals.  But  these 
hypothetical  substances  are  perhaps  merely  the  conditions 
necessary  to  start  a  definite  form  of  motion,  which  acts  as  the 
impetus  in  the  decomposition  of  the  starch-molecule.  A  de- 
velopment of  heat  cannot  be  proved  when  starch  is  broken 
up  by  ferments.  Maly^  even  observed  an  absorption  of  heat. 
This  is  explicable  in  the  following  way :  starch-flour  is  in- 
soluble, whereas  the  products  of  decomposition  are  soluble  in 
water.  Heat  must  be  used  up  in  their  solution,  as  is  always 
the  case  in  the  transit  from  the  solid  to  the  fluid  state.  The 
amount  of  heat  thus  fixed  is  greater  than  that  liberated  by 
decomposition.  That  heat  is  set  free  when  decomposition  takes 
place  follows  of  necessity  from  the  fact  that  the  heat  of  com- 
bustion of  the  maltose  and  dextrin  is  less  than  that  of  an  equiva- 
lent amount  of  starch -flour. 

Hoppe-Seyler  ^  and  his  pupils  *  have  shown  that  formate  of 

*  Eduard  Donath,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  viii.  p.  795 :  1875 ;  vol.  li. 
p.  1089:  1878;  M.  Barth,  ibid.,  vol.  xi.  p.  474:  1878. 

2  Maly,  Pflüger's  Arch.,  vol.  xxii.  p.  Ill :  1880. 

^  Hoppe-Seyler,  Pflüger's  Arch.,  vol.  xii.  p.  4  :  1876. 

*  Leo  Popoff,  Pflüger's  Arch.,  vol.  x.  p.  113 :  1875. 


DIGESTION    IN    THE    INTESTINE  157 

lime,  by  the.  action  of  certain  bacteria,  is  split  up  into  carbonate 
of  lime,  carbonic  acid,  and  hydrogen,  with  absorption  of  water : — 

xH  .OH 

0=0  C==0 

X 

^Ca+2H0H=  >Ca+2H2=CaC03+C02+H50-f  2H2. 


0  .0 


<>=0  C=Ü 

^H  "^HO 

Heat  is  developed  in  this  process.  If  the  bacteria  be  killed  by 
ether,  the  decomposition  continues.  This  ferment  therefore  be- 
haves like  invertin.  Sainte-Claire  Deville  and  Debray  ^  have 
made  the  important  discovery  that  the  same  decomposition  of 
formic  acid  into  carbonic  acid  and  hydrogen  can  be  also  brought 
about  by  finely  divided  iridium,  rhodium,  or  ruthenium,  ob- 
tained in  a  moist  condition  by  reduction.  Platinum  or  palla- 
dium produced  in  the  same  way  had  no  action. 

We  thus  see  that  a  living  cell,  an  organic  substance,  and  a 
metal  all  produce  the  same  effect. 

The  decomposition  of  acetic  acid  into  carbonic  acid  and  marsh- 
gas  is  completely  analogous  to  the  decomposition  of  formic  acid, 
and  occurs  under  the  same  conditions  : — 

.CH3  ^OH 

C=0  C=0 

\Ca+2H0H=  Nca+2CH4=CaC03+C02+H20+2CHi. 

o  o 

c=o  0=0 

^CHj  ^OH 

Heat  must  again  be  set  free  in  this  process,  for  the  heat  of  com- 
bustion of  the  marsh-gas  is  less  than  that  of  an  equivalent 
amount  of  acetic  acid. 

From  all  these  examples  it  may  be  seen  that  we  know 
nothing  further  concerning  the  ferments  than  we  do  about  the 
'  katalytic '  substances.  Their  presence  is  absolutely  essen- 
tial to  bring  about  that  form  of  motion  which  gives  the  im- 
petus to  the  transition  from  an  unstable  arrangement  of  atoms 
into  a  more  stable  one.  We  speak  of  a  katalytic  effect,  when 
the  substance  to  which  this  effect  is  ascribed  happens  to  be  a 

^  H.  Sainte-Claire  Deville  et  H.  Debray,  Comp,  rend.,  vol.  Ixxviii.  2,  p.  1782  : 
1874,  • 


158  LECTUEE    XI 

well-known  inorganic  compound  or  an  element.  If,  on  the 
other  hand,  they  are  unknown  organic  substances,  we  speak 
of  a  fermentative  action.  There  is  at  present  no  reason  for 
assuming  that  there  is  any  essential  difference  between  the 
mode  of  action  of  organized  ferments  —  living  unicellular 
organisms  —  and  non-organized,  '  unformed '  ferments.  We 
may  suppose  that  the  process  of  fermentation  is  the  same  in 
both  cases ;  but  we  know  as  little  concerning  the  action  of 
the  unformed  ferments  as  we  do  concerning  the  organized 
ferments. 

The  decomposition  effected  by  the  organized  ferments  ap- 
pears to  take  place  in  the  substance  of  the  living  cell,  and  the 
energy  liberated  by  the  decomposition  is  utilized  for  the  vital 
processes  of  the  cell.  In  favor  of  this  view  can  be  adduced 
the  fact  that,  in  the  case  of  alcoholic  fermentation,  the  amount 
of  sugar  decomposed  in  the  unit  of  time  is  inversely  propor- 
tional to  the  supply  of  oxygen.  With  a  free  supply  of  oxygen, 
there  are  two  sources  for  the  production  of  the  kinetic  energy 
required  for  the  vital  functions :  decomposition  and  oxidation. 
When  oxygen  is  withdrawn,  one  source  is  closed,  and  the  other 
utilized  the  more.^  This  fact  is  of  far-reaching  importance 
for  the  comprehension  of  the  vital  processes  in  the  higher 
animals.^ 

In  all  fermentations  the  decomposition  is  always  accompa- 
nied by  hydration,  in  consequence  of  which  these  processes  can 
only  take  place  in  presence  of  water.  The  exceptions  to  this 
rule  are  only  apparent.  Thus  in  alcoholic  fermentation,  grape- 
sugar  (CgHj20g)  is  decomposed  iato  2C2lIgO  and  2CO2,  appa- 
rently therefore  without  taking  up  any  water.  But  we  must 
not  forget  that  carbonic  acid  in  watery  solution  must,  like  all 
other  dibasic  acids,  contain  two  HO  radicals : — 

.OH 

Cr^^O     =C02+H20. 

Butyric  acid  fermentation  (CgH.Pg  =  C^H^O^  +200^  +  2H2), 
and  lactic  acid  fermentation  (CgH^jOg  =  2C3lIg03)  also  appear 

^  Brefeld,  Landw.  Jahrb.  v.  Nathusius  u.  Thiel,  Heft.  i. :  1874 ;  Verhandl.  d. 
Würzburger  phys. -med.  Gesellsch.,  N.  F.,  vol.  viii.  p.  96  :  1874  ;  Pasteur,  "  Etudes 
8ur  la  biere,"  chap.  vi.  p.  229  :  Paris,  1876  ;  Hoppe-Seyler,  "  Ueber  die  Einwirkung 
des  Sauerstoffes  auf  Gährungen  "  :  Festschrift,  Strassburg,  1881;  Nencki,  ^rcA. 
/.  exp.  Path.  u.  Pharm.,  vol.  xxi.  p.  299  :  1886. 

2  The  fact  observed  by  A.  Fränkel  (Virchow's  Arch.,  vol.  Ixvii.  p.  283  :  1876), 
that  the  decomposition  by  proteid  goes  on  twice  as  fast  in  dogs  when  their  supply 
of  oxygen  is  diminished,  is  perhaps  of  a  similar  nature.  Compare  also  Herrn. 
Oppenheim,  Pflüger's  Arch.,  vol.  xiiii.  p.  490  :    1880. 


DIGESTION    IN    THE    INTESTINE  159 

to  form  exceptions.  From  analogy  with  other  processes  of  fer- 
mentation, we  must  suppose  that  these  processes  are  also  accom- 
panied by  hydration.  We  must  refer  the  reader  to  the  papers 
of  Hoppe-Seyler  ^  and  Nencki^  for  further  information  on  this 
subject. 

Many  attempts  have  been  made  to  isolate  the  unorganized 
ferments.  It  is  in  fact  possible  to  obtain  precipitates  from  solu- 
tions containing  ferments  which  still  retain  the  characteristic 
fermentative  properties.  But  we  have  no  guarantee  that  these 
precipitates,  which  are  always  amorphous,  are  chemical  entities. 
In  the  cases  in  which  they  have  been  analyzed,  the  composition 
has  been  found  closely  similar  to  that  of  proteids  and  peptones. 
But  we  cannot  ascertain  whether  the  ferment  may  not  form  a 
fraction  of  the  material  analyzed,  so  small  as  not  to  influence 
the  result  of  the  analysis. 

All  ferments  are  soluble  in  water ;  all  may  be  precipitated 
from  their  aqueous  solutions  by  alcohol  or  ammonium  sul- 
phate,^ and  are  again  dissolved  by  water  after  their  precipita- 
tion. Most  of  them  are  also  soluble  in  glycerin,  and  may  be 
precipitated  from  this  solution  by  alcohol.^  All  the  previous 
attempts  at  isolation  mainly  depend  on  these  properties,  which 
are  however  common  to  a  large  number  of  other  constituents 
of  the  tissues ;  so  that  other  means  must  be  found  to  effect  a 
further  separation.  Certain  ferments — such  for  instance  as 
pepsin — do  not  diffuse  through  animal  membranes,^  and  all 
have  a  great  tendency  to  be  carried  down  by  neutral  precipi- 
tates.*' These  properties  have  also  been  utilized  for  the  pur- 
pose of  isolating  ferments.  It  would  lead  us  too  far  to  give 
details  concerning  all  these  procedures.  I  must  refer  you 
to    the    observations    of    Brücke,^    Danilewsky,*    Cohnheim,^ 

^  Hoppe-Seyler,  Pfliiger's  Arch.,  vol.  xii.  p.  14  :  1876. 

*  Nencki,  Journ.f.  prakt.  Chem.,  vol.  xvii.  p.  105 :  1879. 

^  [Invertin  appears  not  to  be  precipitated  by  ammoniuni  sulphate.] 

*  Von  Wittich,  Pfliiger's  Arch.,  vol.  ii.  p.  193 :  1869  ;  and  vol.  iii.  p.  339  : 
1870. 

*  Krasilnikow,  Medicinisky  Wjestnik  :  1864.  Diakonow  gives  a  short  notice 
of  this  work  in  Hoppe-Seyler's  Med.  chem.  Unters.,  p.  241.  See  also  A.  Schöflfer, 
Centralbl.  f.  d.  med.  Wissensch.,  ]p.  641:  1866;  von.  Wittich,  Pfliiger's  Arch., 
vol.  V.  p.  443:  1872;  Olof  Hammarsten,  "  Oni  pepsinets  indifi"usibilitet,"  Upsala 
läkareförennings  forhandlingar,  vol.  yiü.  p.   565:  1873. 

*  Brücke,  Sitzungsber.  d.  Wiener  Akad.,  vol.  xliii.  p.  601 :  1861.  A.  v. 
Heltzl,  "Beiträge  zur  Lehre  der  Verdauungsfermente  des  Magensaftes": 
Dorpat,  1864. 

''  Brücke,  Sitzungsber.  d.  Wiener  Akad.,  vol.  xxxvii.  p.  131 :  1859 ;  and  vol. 
xliii.  p.  601 :  1861. 

*  Danilewsky,  Virchow's  Arch.,  vol.  xxv.  p.  279  :  1862. 

^  J.  Cohnheim,  Virchow's  Arch.,  vol.  xxviii.  p.  241 :  1863. 


160  LECTUEE   XI 

Aug.    Schmidt/    Hüfner/   Maly,^    Kühne/    Barth/    and    O. 

Every  ferment  develops  its  maximum  activity  at  a  definite 
temperature.  This  temperature  must  be  diflFerent  in  the  case 
of  the  digestive  ferments  of  cold-  and  warm-blooded  animals ; 
we  should  expect  this  on  teleological  grounds,  and  it  is  con- 
firmed by  direct  observation.  By  treating  the  gastric  mucous 
membrane  of  a  mammal,  recently  killed,  with  dilute  HCl  (from 
2  to  3  per  1,000),  a  so-called  artificial  gastric  juice  is  obtained 
which  rapidly  peptonizes  all  varieties  of  proteid.  At  an  ordi- 
nary temperature  this  action  is  mostly  very  slight,  and  it  ceases 
entirely  at  about  10°  C.  At  a  temperature  of  0°  C,  not  the 
least  trace  of  digestion  goes  on.  But  Fick  and  Murisier^ 
found  that  the  artificial  gastric  juice,  prepared  from  the 
stomach  of  the  frog,  the  pike,  and  the  trout,  constantly  exerted 
a  peptonizing  influence  even  at  0°.  Hoppe-Seyl er  *  confirmed 
these  results.  He  found  that  artificial  gastric  juice  of  the 
pike  digested  fibrin  more  rapidly  at  15°  C.  than  at  40°,  most 
rapidly  at  about  20°.  A  little  above  0°  the  action  was  slower 
than  at  15°,  but  still  very  marked.  Fick  and  Hoppe-Seyler 
conclude  from  these  observations  that  the  gastric  juice  of 
warm-blooded  contains  a  different  ferment  from  that  of  cold- 
blooded animals. 

Like  pepsin  obtained  from  different  sources,  we  find  that 
the  so-called  diastatic  ferments,  which  decompose  starch,  de- 
velop their  maximum  effects  at  temperatures  which  vary  ac- 
cording to  the  source  from  which  these  ferments  are  derived. 
The  diastatic  ferments  of  the  pancreas  and  saliva  act  most 
quickly  at  from  37°  to  40°  C;  that  of  germinating  barley  at 
from  54°  to  63°  C.^ 

When  aqueous  solutions  containing  ferments  are  heated  to 
more  than  70°  C,  the  unorganized  as  well  as  the  organized 
ferments   are  destroyed.     The  solutions  are  found  to  be  in- 

■^  Aug.  Schmidt,  "  Ueber  Emulsin  und  Legumin,"  Dissert. :  Tübingen,  1871. 

*Hüfner,  Journ.  f.  prakt.  Chem.,  vol.  v.  p.  372:  1872. 

3  Maly,  Pflüger's  Arch.,  vol.  ix.  p.  592  :  1874. 

■*  Kühne,  Verhandl.  des  naturhist.  med.  Vereins  zu  Heidelberg,  vol.  i.:  1876  ; 
and  vol.  iii.  p.  463 :  1886  ;  Kühne  and  Chittenden,  Zeitsehr.  f.  Biol.,  vol.  iv. 
p.  428 :  1886. 

''Barth,  "Zur  Kenntniss  des  Inverting,"  ^er.  der  deutsch,  chem.  Ges.,  vol. 
xi.  p.  474:  1878. 

6  Low,  Pflüger's  Arch.,  vol.  xxvii.  p.  203  :  1882. 

''  Murisier,  Verhandlungen  derphys.  med.  Gesellschaft  zu  Würzburg,  vol.  iv. 
p.  120 :  1873. 

*  Hoppe-Seyler,  Pflüger's  Arch.,  vol.  xiv.  p.  395 :  1877.  Compare  also  M. 
Flaum,  Zeitsehr.  f.  Biol.,  vol.  xxviii.  p.  433  :  1892. 

^  J.  Kjeldahl,  "  Meddelser  fra  Carlsberg  Laboratoriet  Kjöbenhaven"  :  1879  ; 
Maly's  Jahresbericht  für  Thierchemie,  p.  382  :  1879. 


DIGESTION    IN    THE    INTESTINE  161 

operative,  both  at  this  temperature  and  also  when  they  are 
again  cooled  down.  On  the  other  hand,  when  in  a  dry  state, 
the  ferments  may  be  exposed  to  a  very  high  temperature  with- 
out losing  their  power.  Hüfner^  heated  his  dried  pancreatic 
ferment  to  100°  C.  without  causing  it  to  become  ineffectual. 
Alex.  Schmidt  ^  and  Salkowski  showed  that  this  was  also  the 
case  with  pepsin.  Salkowski^  heated  pepsin  to  150°  C,  and 
pancreatic  ferment  and  invertin  to  160°  C.  for  many  hours,  and 
showed  that  they  were  still  active  on  cooling  and  when  mixed 
with  water.  It  was  thought  that  this  would  serve  as  a  means 
of  distinguishing  the  unorganized  from  the  organized  ferments. 
But  more  recent  investigations  have  shown  that  the  spores  of 
certain  bacteria  can  stand  a  temperature  of  from  110°  to  140° 
C  without  losing  life  or  power  of  development.'* 

The  power  of  resisting  absolute  alcohol  has  also  been 
regarded  as  characteristic  of  unformed  ferments,  and  as  dis- 
tinguishing them  from  formed  ferments.  But  the  spores  of 
certain  bacteria  possess  even  this  power.  Koch  ^  showed,  for 
instance,  that  the  spores  of  anthrax  bacilli  could  be  kept  for 
110  days  in  absolute  alcohol  without  being  killed.  On  the 
other  hand,  all  spores  are  apparently  killed  when  subjected  for 
a  long  period,  say  thirty  days,  to  ether — a  treatment  which  has 
not  been  found  to  have  any  effect  on  the  unorganized  ferments. 
Prussic  acid,  chloroform,  benzol,  thymol,  oil  of  turpentine,  and 
sodium  fluorid,^  are  all  supposed  to  act  like  ether  in  killing 
the  organized,  and  in  having  no  effect  upon  the  unorganized, 
ferments. 

After  these  preliminary  remarks  on  ferments  in  general,  we 
will  now  return  to  the  pancreatic  juice  and  its  fermentative 
actions.  I  have  already  mentioned  that  the  pancreatic  juice 
acts  upon  all  the  three  main  groups  of  food-stuffs.  To  explain 
these  three  actions,  it  has  been  assumed  that  there  are  three 
different  ferments,  although  there  is  no  definite  ground  for 
such  an  assumption.      Hüfner,'^  in   his  numerous  attempts  to 

1  Hiifner,  Journ.  f.  prakt.    Chem,.,  vol.  v.  p.  372  :  1872. 

2  Alex.  Schmidt,  Centralbl.  f.  d.  med.  Wissensch.,  No.  29  :  1876. 

^  Salkowski,  Virchow's  Arch.,  vol.  Ixx.  p.  158:  1877;  and  vol.  Ixxxi.  p. 
552 :  1880.  Compare  also  Hiippe,  Mittheil.  d.  Kaiserl.  Gesundheitsamtes,  vol.  i.: 
1881. 

*R.  Koch,  und  Wolffhügel,  Mittheil.  d.  Kaiserl.  Gesundheitsamtes,  vol.  i. : 
Berlin,  1881 ;  Max.  Wolff,  Virchow's  Arch.,  vol.  cii.  p.  81 :  1885. 

5R.  Koch,  "  Ueber  Disinfection,"  Mittheil.  d.  Kaiserl.  Gesundheittamtes, 
vol.  i. :  1881. 

8  M.  Arthus  and  Ad.  Huber,  Arch.  d.  Physiol.,  vol.  xxiv.  p.  651 :  1894. 
Compt.  rend.,  vol.  cxvi.  p.  839:  1894. 

'  Hufner,  Journ.  f.  prakt.  Chem.,  vol.  v.  p.  372 :  1872.  For  the  experiments 
to  isolate  three  different  ferments,  see  Danilewsky,  Virchow's  Arch.,  vol.  xxv.  p. 
279:  1862;  Lossnitzer,  "Einige  Versuche  über  die  Verdauung  der  Eiweiss- 
11 


162  LECTURE   XI 

isolate  the  pancreatic  ferments,  always  obtained  preparations 
which  had  the  threefold  fermentative  action. 

"With  regard  to  the  action  on  carbohydeates,  the  con- 
version of  the  insoluble  starch  flour  has  been  more  particularly 
studied.  The  process  of  starch  digestion  is  by  no  means  as 
simple  as  it  was  formerly  imagined.  Till  quite  recently,  it  was 
considered  that  starch  flour  was  altered  by  the  digestive  fer- 
ments of  the  saliva  and  of  the  pancreatic  juice,  and  by  the 
ferment  of  the  germinating  barley  or  diastase,  in  the  same  way 
as  on  boiling  with  dilute  sulphuric  acid,  when,  as  is  well 
known,  starch  flour  is  by  a  process  of  hydration  completely 
converted  into  grape-sugar  (dextrose),  whilst  dextrin  only  oc- 
curs as  an  intermediate  stage. 

But  more  recent  research  has  shown'  that  the  amount  of 
sugar  produced  forms  but  half  of  the  entire  weight  of  the 
starch,  and  that  this  sugar  is  not  grape-sugar,  but  maltose 
(0^2^22011+  H2O).  The  remainder  is  dextrin,  and  this  dextrin 
cannot  be  converted  into  sugar  by  further  action  of  the  fer- 
ments. It  has  also  been  discovered  that  there  are  two  varieties 
of  dextrin,  of  which  one  is  colored  red  by  iodin,  while  the 
other  remains  colorless.  It  has  been  further  ascertained  that 
a  certain  carbohydrate,  so-called  soluble  starch,  which  also  gives 
a  blue  color  with  iodin,  occurs  as  an  intermediate  product  be- 
tween ordinary  starch  and  the  dextrius.  Finally,  it  has  been 
found  that  even  the  original  starch  flour  is  not  a  chemical  entity, 
but  that  the  concentric  layers  of  the  starch  granule  are  composed 
of  various  carbohydrates  in  different  proportions. 

körper,"  Dissert.:  Leipzig,  1864;  Victor  Paschutin,  Du  Bois'  Arch.,  p.  382: 
1873;  Kühne,  Verhandl.  d.  naturhist.  med.  Ver.  zu  Heidelb.,  N.  F.,  vol.  i. :  1876. 
Heidenhain  and  his  pupil  Podolinski  come  to  tlie  conclusion  that  the  ferment 
which  dissolves  proteid  does  not  exist  preformed  in  the  pancreas,  but  is  formed 
during  secretion  from  a  precursor  present  in  the  gland  (Pfliiger's  Arch.,  vol.  x. 
p.  557  :  1875 ;  and  vol.  xiii.  p.  422 :  1876).  Compare  also  Giov.  Weiss,  Virchow's 
Arch.,  vol.  Ixviii.  p.  413  :  1876. 

^Musculus,  Compt.  rend.,  vol.  1.  p.  785:  1860;  or  Ann.  chim.  et  phys.,  ser. 
iii.  vol.  Ix.  p.  203:  1860;  Compt.  rend.,  vol.  Ixviii.  p.  1267:  1869;  vol.  Ixx.  p. 
857:  1870;  vol.  Ixxviii.  2,  p.  1413:  1874;  Ann.  chim.  et  phys.,  ser.  v.  vol.  ii.  p. 
385  :  1874  ;  Payen,  Ann.  chim.  et  phys.,  ser.  iv.  vol.  iv.  p.  286 :  1865  ;  L.  Coutaret, 
Compt.  rend.,  vol.  Ixx.  p.  382:  1870;  Aug.  Schwarzer,  Journ.  f.  prakt.  Chem., 
N.  F.,  vol.  i.  p.  212 :  1870 ;  E.  Schulze  u.  Märker,  Dingler's  Polytechnisches 
Journ.,  vol.  ccvi.  p.  245 :  1872 ;  Brücke,  Sitzungsberichte  d.  Wiener  Akad.,  vol. 
Ixv.  part  iii.  p.  126 :  1872 ;  C.  O'SulIivan,  Journ.  of  Chem.  Soc,  ser.  ii.  vol.  x.  p. 
579:  1872;  E.  Schulze,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  vii.  p.  1048:  1874; 
Nägeli,  "Beiträge  zur  Kenntniss  der  Stärkegruppe":  Leipzig,  1874;  O.  Nasse, 
Pflüger's  Arch.,  vol.  xiv.  p.  473:  1877.  Musculus  und  v.  Mering,  Zeitschr.  f. 
physiol.  Chem.,  vol.  i.  p.  395:  1878;  and  vol.  ii.  p.  403:  1878;  Musculus  und  G. 
Gruber,  Zeitschr.  f.  physiol.  Chem..,  vol.  ii.  p,  177:  1878.  Compare  also  the  re- 
view of  works  by  v.  Mering,  Du  Bois'  Arch.,  pp.  389-395 :  1877. 


DIGESTION    IN   THE    INTESTINE  163 

The  final  products  of  the  decomposition  of  starch  are,  at 
any  rate,  different  in  the  living  organism  to  those  produced  by 
artificial  digestion  outside  the  body ;  the  starch  appears  to  be 
completely  converted  into  grape-sugar.  Even  in  long-con- 
tinued artificial  pancreatic  digestion  of  starch,  grape-sugar 
(dextrose)  always  occurs  together  with  maltose.^  Maltose  and 
dextrin  cannot  be  found  in  the  blood  and  in  the  tissues,^  and  in 
the  case  of  diabetic  patients,  who  are  unable  to  destroy  the 
carbohydrates,  grape-sugar  alone  appears  in  the  urine  after 
starch  has  been  eaten. 

We  know  as  little  concerning  the  changes  that  cellulose 
undergoes  in  the  intestine  as  we  do  concerning  the  fate  of 
dextrin.  Outside  the  body,  cellulose  is  neither  altered  by  the 
pancreatic  juice  nor  by  any  other  digestive  secretion.  But, 
as  a  fact,  a  large  portion,  as  we  have  already  seen,  disap- 
pears in  the  intestine.  I  imagine  that  it  is  a  fermentative 
action  which  enables  the  epithelial  cells  of  the  intestine  to  dis- 
solve the  cellulose,  and  perhaps  also  to  convert  the  dextrin  into 
sugar.  This  power  has  frequently  been  observed  in  unicellular 
bodies.  I  may  refer  to  the  behavior  of  the  Vampyrella,  which 
has  already  been  described  (p.  3),  and  which  dissolves  the 
cellulose  wall  of  the  algge.  A  few  authors  have  adopted  the 
view  that  the  cellulose  is  not  made  use  of  in  our  body  at  all  as 
food,  but  is  split  up  by  parasitic  bacteria  in  our  intestines  into 
carbonic  acid  and  marsh  gas.  That  such  a  decomposition  of 
cellulose  by  bacteria  does  take  place  has  been  incontestably 
proved  by  Hoppe-Seyler's  experiments,^  which  render  it  prob- 
able that  it  also  occurs  in  the  alimentary  canal. ^  But  it  is 
doubtful  whether  all  the  cellulose  that  disappears  in  the  ali- 
mentary canal  is  split  up  in  this  manner.^ 

The  pancreatic  juice  exercises  a  fermentative  action  on 
FATS  similar  to  that  on   carbohydrates ;  decomposition   takes 

^  Musculus  und  v.  Mering,  Zeitschr.  f.  physiol.  Chem.,  vol.  ii.  p.  403  :  1879  ; 
Horace  T.  Brown  and  John  Heron,  Leibig's  Annal.,  pp.  204,  228 :  1880. 

2  Intimation  of  the  occurrence  of  colloid  carbohydrates  in  the  blood  of  the 
portal  vein  may  be  found  in  v.  Mering's  paper.  Du  Bois'  Arch.,  p.  413:  1877; 
and  in  another  by  A.  M.  Bleile,  Du  Bois'  Arch.,  p.  70 :  1879.  But  only  very 
small  quantities  are  concerned,  and  perhaps  even  these  only  occur  occasionally. 
Bleile's  experiments  prove  that  the  chief  part  of  the  dextrin  is  converted  into 
sugar,  as  he  observed  that,  after  an  exclusive  diet  of  dextrin,  the  amount  of  sugar 
in  the  portal  blood  increases. 

*  Hoppe-Seyler,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  ivi.  p.  122  :  1883 ;  and 
Zeitschr.  f.  physiol.  Chem.,  vol.  x.  p.  404:  1886. 

■*  H.  Tappeiner,  Zeitschr.  f.  Biolog.,  vol.  xx.  p.  52  :  1884 ;  and  vol.  xxiv.  p. 
105:  1888. 

^  Compare  H.  Weiske,  Chem.  Centralhl.,  vol.  xv.  p.  385 :  1884 ;  Henneberg 
and  Stohmann,  Zeitschr.  f.  Biolog.,  vol.  xii.  p.  613  :  1885  ;  F.  Lehmann,  Journ. 
f.  Landw.,  vol.  xxxvii.  p.  251 :  1889  ;  Alf.  Mallevre,  Pfliiger's  Arch.,  vol.  xlix, 
p.  460 :  1891 ;  Zuntz,  ihid.,  vol.  xlix.  p.  477 :  1891. 


164  LECTURE    XI 

place  with  hydration.  The  fats  are  well  known  to  be  com- 
pound ethers,  combinations  of  a  trivalent  alcohol,  glycerin, 
with  three  molecules  of  monobasic  acids,  principally  stearic 
acid,  palmitic  acid,  and  oleic  acid.  Beside  which,  certain  fats 
contain  small  quantities  of  volatile  fatty  acids,  such  as  butyric 
acid  in  the  fats  of  milk.  By  the  action  of  the  pancreatic 
ferment,  the  fat  molecule  takes  up  three  molecules  of  water, 
and  splits  up  into  glycerin  and  into  three  molecules  of  fatty 
acid.  This  action  of  the  pancreatic  juice  was  discovered  by 
Bernard.^  How  large  a  portion  of  the  fats  is  thus  broken  up 
in  the  intestine  cannot  be  stated,  but  it  is  probably  a  very  small 
one.  For  the  decomposition  of  fats,  at  least  in  experiments  on 
artificial  digestion,  goes  on  very  slowly,  whereas  the  absorption 
of  fats  proceeds  very  rapidly.  But  it  is  quite  sufficient  if  only 
a  minute  part  of  the  fats  is  split  up,  for  the  whole  amount 
of  fat  is  thereby  rendered  capable  of  being  converted  into  a 
fine  emulsion,  in  which  form  it  passes  through  the  intestinal 
wall. 

The  emulsification  of  fats  is  brought  about  in  the  following 
manner.  It  is  well  known  that  the  neutral  fats  can  only  be 
saponified,  i.  e.,  split  up  into  glycerin  and  salts  of  fatty  acids  to 
form  soaps,  by  free  alkalies.  Carbonates  of  the  alkalies  have 
no  action  on  neutral  fats  but  only  on  free  fatty  acids ;  the 
carbonic  acid  is  driven  out  of  the  salts  by  the  stronger  acid, 
and  a  salt  is  formed  by  the  combination  of  the  fatty  acid  with 
alkali.  Fatty  acids  and  neutral  glycerides  are  intimately 
miscible  in  every  proportion.  In  such  a  mixture  of  fat  and  a 
small  quantity  of  fatty  acid,  the  molecules  of  the  fatty  acid  are 
thus  always  to  be  found  among  the  molecules  of  the  neutral 
glycerids.  If  a  solution  of  carbonate  of  soda  act  upon  this 
mixture,  a  soapy  solution  is  formed  everywhere  between  the 
molecules  of  the  neutral  fats.  By  this  means  the  whole  mass 
of  fat  is  immediately  converted  into  a  fine  emulsion  of  micro- 
scopically small  drops.  Perfectly  fresh  neutral  fat  cannot  be 
emulsified  by  a  solution  of  carbonate  of  soda.  If,  on  the  other 
hand,  rancid  fat  be  taken,  i.  e.,  fat  in  which  a  part  of  the  fatty 

^  Bernard,  Ann.  de  Chim.  et  de  Physique,  ser.  iii.  t.  xxv.  p.  474  :  1849.  Com- 
pare also  Ogata,  Du  Bois'  Arch.,  p.  515  :  1881.  According  to  this  investigation, 
which  was  carried  out  in  Ludwig's  laboratory,  the  decomposition  of  the  fats  be- 
gins already  in  the  stomach.  Marcet  had  previously  come  to  the  same  conclusion 
(Medical  Times  and  Gazette,  new  ser.,  vol.  xvii.  p.  210:  1858).  The  decomposi- 
tion of  fats  in  the  stomach  is  probably  effected,  not  by  an  unorganized  ferment 
of  the  gastric  juice,  but  by  putrefactive  organisms.  The  cause  of  the  decompo- 
sition of  fats  in  artificial  pancreatic  digestion  has  been  so  interpreted.  But 
Nencki's  latest  experiments  (Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xx.  p.  373: 
1886)  show  that  the  pancreatic  ferment  decomposes  as  much  fat  if  phenol  be 
present  as  if  there  were  no  antiseptic. 


DIGESTION    IN    THE    INTESTINE  165 

acids  has  already  been  set  free  by  the  action  of  putrefactive 
ferments,  or  if  a  small  amount  of  free  fatty  acids  be  added  to 
the  neutral  fat,  the  emulsion  is  at  once  formed.  When  rancid 
oil  is  poured  on  to  a  dilute  solution  of  sodium  carbonate,  the 
two  layers  of  fluid  combine  directly  they  are  gently  shaken,  and 
the  whole  is  converted  into  an  opaque,  uniform,  and  milky- 
looking  liquid.  Under  the  microscope  the  fat  is  seen  distributed 
in  minute  drops. 

There  are  other  alkaline  salt  solutions  which  can,  like  the 
carbonates  of  soda  or  of  potash,  combine  with  free  fatty  acids 
to  form  soaps.  Such,  for  instance,  is  the  phosphate  of  soda 
with  the  formula  NagHPO^.  This  salt  with  fatty  acids  gives 
soap  and  acid  phosphate  of  sodium,  NaHgPO^.  As  we  shall 
soon  see,  the  bile,  which  contains  alkaline  salts,  acts  in  a 
similar  manner  on  fatty  acids.^  The  emulsions,  which  are 
formed  by  means  of  bile,  are  however  very  temporary. 

Carbonate  of  soda  is  contained  in  the  pancreatic  secretion, 
for  the  analysis  ^  of  the  ash  shows  that  the  secretion  contains 
more  sodium  than  is  necessary  for  the  saturation  of  the  strong 
mineral  acids  present.  Two  weak  acids  divide  the  remainder 
among  themselves :  proteid  and  carbonic  acid.  The  intestinal 
juice  is  likewise  very  rich  in  carbonate  of  soda,  as  we  shall  soon 
see.  By  the  action  of  these  alkaline  secretions  the  fat  is 
emulsified  in  minute  particles  which,  as  previously  described 
(p.  164),  are  passed  on  to  the  commencement  of  the  chyle- 
vessels  by  the  active  intervention  of  the  epithelial  cells. 

The  mechanism  of  fat  absorption  is  not  however  entirely 
explained  by  the  above-mentioned  facts.  Some  other  unknown 
part  must  be  played  by  the  pancreatic  juice  in  this  process, 
since  after  extirpation  of  the  pancreas  in  dogs  the  absorption 
of  fat  is  entirely  abolished,  although  the  greater  part  is  split  up 
into  fatty  acids  and  glycerin,  probably  by  bacterial  putrefaction. 
All  the  fat  eaten  by  the  dogs  can  be  recovered  from  the  feces, 
partly  unchanged,  but  for  the  most  part  as  free  fatty  acids  and 
soaps.     If  some  pig's  pancreas  be  given  to  the  dogs  along  with 

1  The  emulsifying  action  of  alkaline  salt  solutions  has  long  been  known  to 
technical  chemists ;  it  is  practically  employed  in  dyeing  articles  Turkey  red. 
Marcet  was  the  first  to  draw  attention  to  its  physiological  bearing  {Medical 
Times  and  Gazette,  new  ser.,  vol.  xvii.  p.  209  :  1858).  Also  Brücke,  Sitzungsber. 
d.  Wiener  Akad.  Math.-nat.  Classe,  vol.  Ixi.  part  ii.  p.  362 :  1870.  Compare  also 
J.  Steiner,  Du  Bois'  Arch.,  p.  286 :  1874 ;  Joh.  Gad,  ibid.,  p.  181 :  1878 ;  Georg 
Quincke,  Pfliiger's  Arch.,  vol.  xix.  p.  129 :  1879 ;  and  Max  v.  Frey,  Du  Bois' 
Arch.,  p.  382  :  1881. 

2 Bidder  and  Schmidt,  "Die  Verdauungssäfte  u.  der  Stoffwechsel,"  p.  245  : 
Mitau  and  Leipzig,  1852.  The  sulphuric  acid  given  in  the  analysis  must  not  be 
taken  into  consideration,  because  it  was  produced  from  the  sulphur  of  the  Pro- 
teids only  in  incineration. 


166  LECTURE    XI 

the  fat,  a  portion  of  the  latter  is  absorbed.^  Moreover,  Claude 
Bernard  has  already  shown  that  a  pancreatic  emulsion  differs 
from  other  emulsions  in  that  it  is  not  destroyed  by  a  slightly 
acid  medium. 

It  now  only  remains  to  consider  the  action  of  the  pancreatic 
secretion  on  the  third  main  group  of  food-stuffs,  the  Proteids. 
By  the  action  of  the  pancreatic  ferment,  as  well  as  that  of  the 
gastric  ferment,  the  proteids  lose  their  colloid  character ;  they 
become  diffusible,"  and  are  no  longer  coagulable ;  they  are 
converted  into  peptones.  The  gelatin-yielding  substances 
undergo  a  similar  alteration ;  they  become  dissolved,  and  the 
solutions  lose  the  power  of  forming  a  jelly  in  the  cold.^ 

The  peptonizing  action  of  the  pancreatic  juice  was  for  a 
long  time  doubted,  until  Corvisart  *  decided  the  matter  in  the 
affirmative.  Kühne,  who  was  present  at  Corvisart's  experi- 
ments, afterwards  carried  out  a  series  of  exhaustive  experi- 
ments on  the  subject  in  Germany.^  Kühne  obtained  the 
secretion  from  eleven  dogs  with  a  temporary  pancreatic  fistula, 
and  he  found  that  "amazing  quantities  of  boiled  fibrin  and 
proteid  were  dissolved  by  the  juice  without  any  trace  of  putre- 
faction, in  from  half  an  hour  to  three  hours,  at  a  temperature 
of  40°  C,  so  that  the  larger  portion  was  converted  into  a  sub- 
stance not  coagulable  at  boiling  heat,  which  was  readily  dif- 
fusible through  vegetable  parchment." 

When  a  fresh  pancreas  was  cut  up  into  small  pieces  with 
scissors,  mixed  with  a  large  quantity  of  fibrin  and  water  heated 
to  40°  C,  and  left  to  stand  from  three  to  six  hours,  the 
gland  disappeared  with  the  fibrin,  leaving  but  a  trace  behind. 
The  reaction  after  complete  solution  was  alkaline.  Only  a 
small  portion  of  the  decomposed  proteid  could  be  precipitated 

'  M.  Abelmann,  "  Ueb.  d.  Ausnützung  d.  Nahrungsstoflfe  nach  Pankreas- 
exstirpation."  Dissert. :  Dorpat,  1890.  Compare  also  Vaughan  Harley,  Journ. 
Physiol.,  vol.  xviii.  p.  1 :  1895  ;  E.  Hedon  and  J.  Ville,  Arch.  d.  Physiol.,  p. 
606 :  1897  ;  and  Hedon,  ibid.,  p.  622.  [It  should  be  mentioned  here  that,  accord- 
ing to  most  authorities  at  the  present  time,  the  greater  proportion  at  any  rate  of 
the  fat  is  absorbed  by  the  intestinal  wall,  not  in  a  particulate  condition  but  in  so- 
lution, either  as  fatty  acid  or  as  soap.  The  chief  function  of  the  bile  seems  to  be 
to  act  as  a  solvent  of  these  two  classes  of  bodies,  and  therefore  as  a  carrier  of 
them  into  the  intestinal  mucous  membrane,  where  they,  with  the  glycerin,  are 
recombined  to  form  neutral  fats.] 

2  The  proofs  of  the  power  of  ready  diffusion  possessed  by  peptones  have  been 
disputed.    See  von  Wittich,  Berliner  klin.  Wochetischr.,  No.  37  :  1872. 

^See  Fr.  Hofmeister,  Zeitschr.  f.physiol.  Chem.,  vol.  ii.  p.  299:  1878.  An 
account  of  the  older  literature  will  also  be  found  here. 

*  Corvisart,  "  Sur  une  fonction  peu  connue  du  pancreas ;  la  digestion  des 
aliments  azotees,"  Gaz.  hehdom.,  Nos.  15,  16,  19 :  1857. 

^  W.  Kühne,  Virchow's  Arch.,  vol.  xxxix.  p.  130 :  1867. 


DIGESTION    IN    THE    INTESTINE  167 

by  acetic  acid  and  by  boiling.^  The  solution,  when  filtered, 
was  concentrated  at  from  60°  to  70°  C.  to  one-sixth  of  its 
volume  and  mixed  with  95  per  cent,  of  alcohol.  This  precipi- 
tated the  peptones  in  flocculent  masses.  When  the  filtered  so- 
lution was  concentrated  and  cooled  down,  tyrosin  first  separated 
out  in  crystals;  then,  on  further  concentration,  leucin  crystal- 
lized out,  in  clumps — "  leucin  cones." 

382  parts  of  dried  fibrin  and  14.2  parts  of  dried  pancreas 
yielded — 

11.0  undissolved  remainder  1  co  c 

42.0  coagulated  proteid         / 
211.2  peptone  ") 

13.3  tyrosin    V  256.1 

31.6  leucin     j 
397.2  —  53.5  —  343.7  dissolved  proteid. 


From  this  it  appears  that  100  parts  of  fibrin  gave  61  of  pep- 
tone, 3.9  of  tyrosin,  9.1  of  leucin,  and  26  of  products  that  we 
are  at  present  unacquainted  with.^ 

It  might  be  supposed  that  the  amido-acids,  leucin  and 
tyrosin,  are  not  split  off  from  the  proteid  molecule  by  the 
action  of  a  pancreatic  ferment,  but  by  the  fermentative  action 
of  putrefactive  organisms.  The  pancreas  and  its  juice  are 
substances  eminently  prone  to  putrefaction,  and  the  alkaline 
reaction  is  favorable  to  the  development  of  putrefactive  or- 
ganisms. It  is  this  liability  to  putrefaction  which  makes  it 
so  much  more  difficult  to  carry  out  experiments  on  artificial 
pancreatic  digestion  that  on  gastric  digestion.  We  know,  in 
fact,  that  peptones  and  amido-acids  are  formed  from  proteids 
by  the  action  of  putrefactive  organisms.  But  Kühne  meets 
this  objection  by  experiments,^  which  were  carried  out  with 

^  For  an  account  of  the  globulin,  acid  albumin,  parapeptone,  propeptone, 
albumoses,  &c.,  which  occur  in  the  conversion  of  proteid  into  peptone,  both  in 
pancreatic  and  gastric  digestion,  see  Meissner,  Zeitschr.  f.  rat.  Med.,  III.  Eeihe. 
vol.  vii.  p.  1 :  1859  ;  Brücke,  Sitzungsber.  der  Wiener  Akad.,  vol.  xxxvii.  p.  131 : 
1859;  Kühne  and  Chittenden,  Zeitschr.  f.  Biolog.,yd\.  xix.  p.  159:  1883;  vol. 
XX.  p.  11 :  1884 ;  vol.  xxii.  p.  409  :  1886 ;  R.  Herth,  3fonatshefte  f.  CJiem.,  vol.  v. 
p.  266  :  1884;  Kühne,  Verhandl.  d.  nat.  w-ed.  Vereins  zu  Heidelb.,  N.  F.,  vol.  iii. 
p.  286 :  1885 ;  Schmidt-Mülheim,  Du  Bois'  Arch.,  p.  36 :  1880  ;  Hans  Thierfelder, 
Zeitschr.  f.  physiol.  Chem.,  vol.  x.  p.  577:  1886;  E..  Neumeister,  Zeitschr.  f. 
Biolog.,  vol.  xxiii.  pp.  381,  402:  1887;  and  "  Ueb.  d.  nächste  Einwirk,  ges- 
pannter Wasserdämpfe  auf  Proteine,"  &c. :  München,  1889;  E.  P.  Pick,  "Zur 
Kenntniss  d.  peptischen  Spaltungsprodukte  des  Fibrins,"  Zeitschr.  f.  physiol. 
ehem.,  vol.  xxviii.  p.  219  :  1899. 

2  [Among  these  products  are  to  be  found  the  same  substances  as  those  which 
occur  in  the  disintegration  of  proteids  by  strong  acids,  e.  g.,  glutamic  and  aspartic 
acids,  as  well  as  the  hexone  bases,  argenin,  lysin,  and  histidin.] 

*  Kühne,  Verhandl.  d.  naturhistor.  med.  Vereins  zu  Heidelb.,  N.  F.,  vol.  i. 
Heft  iii.:  1876. 


168  LECTURE    XI 

the  use  of  salicylic  acid  as  an  antiseptic.  He  showed  that 
concentrated  salicylic  acid,  while  arresting  the  development  of 
putrefactive  germs,  does  not  inhibit  the  action  of  the  pan- 
creatic ferment,  and  that  amido-acids  are  still  formed  under 
these  conditions. 

Kühne  is  of  opinion  that  amido-acids  are  also  formed  in 
the  intestine  of  living  animals.  He  tied  the  intestine  of  a  live 
dog  above  the  entrance  of  the  pancreatic  duct,  and  again  four 
feet  lower  down,  introduced  canulse  at  the  upper  and  lower  ex- 
tremities of  the  intestine  he  had  tied,  and  passed  a  stream  of 
water  heated  to  40°  C.  through  it  until  it  was  quite  clean. 
Fibrin  was  then  put  in  the  piece  of  intestine,  and  the  wound  in 
the  abdomen  was  closed.  The  dog  was  killed  after  four  hours, 
and  the  piece  of  intestine  cut  out.  Among  the  contents  were 
found  peptone,  tyrosin,  and  leucin. 

It  may  be  ä  jpriori  doubted  on  teleological  grounds, 
whether  under  normal  conditions  the  amount  of  amido-acids 
formed  in  the  intestine  is  a  large  one.  It  would  be  a  waste 
of  chemical  potential  energy,  which  would  serve  no  purpose 
when  converted  into  kinetic  energy  by  their  decomposition, 
and  a  reunion  of  the  products  of  such  a  profound  decomposition 
outside  the  intestinal  wall  is  highly  improbable.  And  indeed 
Schmidt-Mülheim,^  in  numerous  experiments  on  the  intestinal 
contents  of  dogs  fed  on  meat,  could  find  only  traces  of  amido- 
acids  or  else  none  at  all.  In  the  same  way  Nencki  found 
neither  leucin  nor  tyrosin  in  the  intestinal  contents  obtained 
from  the  fistula  of  the  lower  end  of  the  small  intestine  in  the 
case  previously  mentioned.^ 

On  boiling  proteids  with  dilute  acids  and  alkalies,  peptones 
again  appear  at  first,  and  amido-acids  later  on. 

We  will  now  inquire  into  the  nature  of  the  process  by  which 
proteid  is  converted  into  peptone. 

As  peptone  occurs  as  an  intermediate  stage  in  the  forma- 
tion of  such  decomposition-products  as  amido-acids  from 
proteid,  it  may  reasonably  be  imagined  that  the  peptones  are 
the  first  immediate  products  of  decomposition.  This  view  is 
further  confirmed  by  the  analogy  of  fermentative  action  and  of 
the  action  of  acids  and  alkalies  on  complex  organic  compounds 
of  known  composition.  In  all  these  processes  disintegration 
is  accompanied  by  hydration.  The  same  pancreatic  ferment 
which,  accompanied  by  hydration,  splits  up  the  fats  into 
glycerin   and   fatty  acids,   and    starch    flour  into   dextrin   and 

1  Schmidt-Mülheim,  Du  Bois'  Arch.,  p.  39  :  1879. 

^  Macfadyen,  Nencki,  and  Sieber,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol. 
xxviii.  p.  323  :  1891. 


DIGESTION    IN    THE    INTESTINE  169 

sugar — thie  same  ferment  also  changes  the  proteids  into  pep- 
tones. What  is  more  natural  than  to  conclude  that  the  pep- 
tones are  also  formed  from  the  proteids  by  a  process  of  decom- 
position accompanied  by  hydration  ? 

It  is  a  very  seductive  theory  to  assume  that  the  colloid  and 
insoluble  proteids  are  polymeric  products  of  the  soluble  pep- 
tones, just  as  the  colloid  and  insoluble  carbohydrates,  such  as 
glycogen,  gum,  starch,  or  cellulose,  are  polymeric  products  of 
the  soluble  sugars,  and  that  the  peptone  molecules  after  absorp- 
tion are  again  combined  into  proteid  molecules,  just  as  the  sugar 
molecules  are  united  to  form  glycogen  in  animal  tissues,  or 
starch  and  woody  fiber  in  vegetable  tissues.  But  it  must  be 
remembered  that  this  theory  is  only  based  upon  analogy.  At 
present  nothing  certain  is  known  about  the  nature  of  peptones. 
It  is  not  known  whether  the  peptones  are  decomposition-prod- 
ucts of  proteid,  or  even  whether  the  decomposition-products 
themselves  are  alike  or  differ  from  each  other,  or  whether  the 
peptones  have  arisen  from  proteid  either  by  a  rearrangement  of 
atoms  without  alteration  of  the  size  of  the  molecules,  or  by 
hydration. 

In  experiments  on  the  composition  of  peptones,  the  error 
has  always  been  made  of  using  impure  material.  The  proteid 
chosen  for  the  production  of  peptone  has  generally  been  the 
fibrin  of  the  blood  (compare  Lecture  XIV.).  We  do  not  know 
how  many  different  proteids  there  are  in  the  coagulum  of 
fibrin  ;  but  we  know  for  certain  that  the  nuclei  and  remains  of 
the  broken-up  leucocytes,  as  well  as  whole  leucocytes  and  the 
stromata  of  red  blood-corpuscles,  are  all  contained  in  this  coag- 
ulum. This  method  of  subjecting  a  conglomeration  of  sub- 
stances and  organisms  to  elementary  analysis,  and  of  after- 
wards comparing  the  result  of  the  analysis  of  a  mixture  of  the 
products  of  our  experiment,  can  lead  to  no  satisfactory  conclu- 
sions. But  this  is  the  type  of  some  of  the  most  exact  work 
on  peptone.^  Now  that  we  are  in  a  position  to  produce  crys- 
talline proteid  compounds,  all  experiments  on  the  composi- 
tion of  peptones  which  are  made  on  other  material  are  utterly 
worthless. 

As  it  has  not  been  found  possible  to  crystallize  the  peptones 
from  their  solutions,  or  to  produce  compounds  capable  of  crys- 
tallization, or  even  compounds  of  constant  composition,  Maly  ^ 
has  adopted  the  method  of  fractional  precipitation,  in  order 
to  decide  the  question  whether  the  peptone  solution,  obtained 
from  the  blood-fibrin  by  artificial  pepsin   digestion,  contains 

*  Compare  R.  Maly's  critique  in  Pfliiger's  Arch.,  vol.  xx.  p.  315 :  1879. 
2  R.  Maly,  Pflüger's  Arch.,  vol.  ix,  p.  585 :  1874. 


170  LECTUEE   XI 

a  single  peptone  or  a  mixture  of  different  peptones.  Maly 
treated  the  clear  and  highly  concentrated  peptone  solution 
with  strong  alcohol,  until  a  portion  of  the  peptone  separated 
out  in  flocculent  masses  (fraction  1);  the  filtrate  was  again  pre- 
cipitated out  with  alcohol  (fraction  2)  ;  and,  finally,  the  remain- 
ing alcoholic  solution  was  evaporated  to  dryness  (fraction  3). 
If  the  peptone  solution  contained  several  different  peptones,  we 
should  expect  to  find  that  the  various  fractions  possessed  a 
varying  composition ;  for  we  cannot  assume  that  the  different 
peptones  have  the  same  power  of  dissolving  in  dilute  alcohol. 
Maly  found  that  the  figures  were  so  nearly  the  same  in  the  ulti- 
mate analysis  of  his  three  fractions,  that  he  came  to  the  con- 
clusion that  only  one  peptone  was  formed.  Maly's  pupil, 
Herth,^  came  to  the  like  conclusion,  from  experiments  carried 
out  on  the  same  principle  with  solutions  of  peptone  obtained 
from  egg-albumin. 

Maly's  and  Herth's  figures  have  not  convinced  me  of  the 
justice  of  this  conclusion.  It  is  particularly  to  be  regretted 
that,  in  the  ultimate  analyses,  the  amounts  of  sulphur  in  the 
fractional  precipitations  were  not  determined.  We  should  most 
readily  have  expected  to  see  a  difference  in  the  amount  of  sul- 
phur. If  we  regard  the  proteids  as  compounds  of  the  pep- 
tones, we  must  assume  that  there  are  several  peptones,  some 
rich  and  some  poor  in  sulphur,  or  else  some  containing  sul- 
phur and  others  without  any  sulphur,  for  the  reason  that  the 
amount  of  sulphur  in  the  different  kinds  of  proteid  varies  so 
remarkably.  But  if,  on  the  other  hand,  we  do  not  regard 
the  peptones  as  produced  by  the  splitting  of  the  proteid  mole- 
cule, we  must  assume  as  many  different  peptones  as  there  are 
proteids  of  varying  composition.  There  are,  at  any  rate,  sev- 
eral peptones.  A.  Krüger  ^  has  recently  made  analyses  of  pro- 
teid and  peptones,  in  which  he  has  bestowed  especial  care 
upon  the  estimation  of  sulphur ;  but  unfortunately,  instead  of 
using  pure  material,  he  employed  fibrin  and  egg-albumin.  The 
latter,  like  the  proteid  of  blood-serum  (vide  Lecture  XIV.),  is 
a  mixture  of  at  least  two  different  kinds  of  proteid,  a  globulin 
and  an  albumin. 

The  quantitative  estimates  of  the  amounts  of  carbon,  hy- 
drogen, and  nitrogen  in  the  purest  of  the  peptone  prepara- 
tions   hitherto    made,  have   always   given    figures    which    are 

^  Robert  Herth  (Maly's  laboratory  in  Graz),  Zeitschr.  f.  physiol.  Chem.,  vol. 
i.  p.  277  :  1887.  Compare  also  A.  Henninger,  "  De  la  nature  et  du  role  physio- 
logique  des  peptones":  Paris;  Compt.  rend.,  vol.  Ixxxvi.  pp.  1413,  1464:  1878. 

2  Albert  Krüger,  Pfliiger's  Arch.,  vol.  xliii.  p.  244:  1888.  This  paper  con- 
tains a  summary  of  the  earlier  literature  on  the  amount  of  sulphur  in  the  various 
kinds  of  proteid  and  the  different  ways  in  which  sulphur  is  combined. 


DIGESTION    IN    THE    INTESTINE  171 

within  th^  limits  between  which  the  composition  of  proteid 
varies.^ 

Whether  all  proteid,  in  order  to  become  absorbed,  must  be 
previously  peptonized,  or  whether  a  part  is  taken  up  unaltered ; 
whether  the  peptones  are  again  reconverted  into  proteid  after 
absorption,  and  where  this  conversion  takes  place; — are  ques- 
tions which  will  be  treated  more  in  detail  in  Lecture  XIII., 
after  we  have  become  acquainted  with  the  parts  played  by  the 
remaining  digestive  secretions,  the  intestinal  juice  and  the  bile. 

^  The  divergence  in  the  results  recently  obtained  by  Kühne  and  Chittenden 
awaits  further  investigation  {Zeitschr,  /.  Biolog.,  vol.  xxii.  p.  423  :  1886).  It  was 
attempted  to  obtain  further  insight  into  the  nature  of  peptones  by  comparative 
experiments  on  the  optical  characteristics  of  the  proteids  and  peptones,  on  their 
refractive  power,  and  their  behavior  towards  polarized  light.  But  these  inves- 
tigations have  not  led  to  any  unanimous  or  conclusive  results  (see  J.  Bechamp, 
Compt.  rend.,  vol.  xciv.  p.  883  :  1882 ;  A.  Poehl,  "  Ueber  des  Vorkommen  u.  die 
Bildung  des  Peptons  ausserhalb  des  Verdauungsapparates  u.  über  die  Rück- 
bildung des  Peptons  in  Eiweiss,"  Dorpater  Dissert. :  St.  Petersburg,  Röttger, 
1882;  and  Ber.  d.  deutsch,  ehem.  Ges.,  p.  1152:  1883).  The  fact  observed  by 
Danilewski,  that  the  heat  of  combustion  of  the  peptones  is  less  than  that  of  the 
proteids  {Centralbl.f.  d.  med.  Wissensch.,  Nos.  26  and  27 :  1881),  can  also  be  in- 
terpreted in  several  ways.  This  fact  agrees  with  the  decomposition  hypothesis 
just  as  well  as  with  the  theory  that  hydration  is  the  essence  of  peptonization.  It 
has  been,  moreover,  quite  lately  noted  that  the  peptones  could  be  reconverted 
into  proteids  by  the  action  of  dehydrating  agents.  But  all  these  statements  bear 
the  character  of  preliminary  communications.  They  are  not  therefore  suitable 
for  critical  discussion  in  a  text-book.  See  Henninger,  Compt.  rend.,  vol.  Ixxxvi. 
p.  1464:  1878;  Hofmeister,  Zeitschr.  f.  physiol.Chem.,  vol.  ii.  p.  206:  1878;  and 
vol.  iv.  p.  267:  1880;  Danilewski,  Centralbl.f.  d.  med.  Wissensch.,  No.  42:  1880; 
Schmidt-Mülheim,  Du  Bois'  Arch.,  p.  36:  1880;  A.  Poehl,  loc.  cit.,  and  Ber.  d. 
deutsch,  ehem.  Ges.,  p.  1355  :  1881 ;  p.  1163  :  1883.  Compare  also  O.  Loew,  Pflüger's 
Arch.,  vol.  xxxi.  p.  405 :  1883 ;  and  R.  Neumeister,  Zeitschr.  f.  Biolog.,  vol. 
xxiii.  p.  394 :  1887. 


LECTURE   XII 


INTESTINAL    JUICE    AND    BILE 


Thiey,^  bj  his  bold  vivisection,  was  the  first  to  obtain  and 
examine  the  intestinal  juice,  the  secretion  of  Lieberkühn's 
glands,  in  a  pure  state.  Thiry  opened  the  abdomen  of  dogs, 
after  they  had  fasted  for  twenty-four  hours,  by  an  incision  in 
the  linea  alba.  A  coil  of  small  intestine  was  drawn  out,  and 
a  piece  from  10  to  15  cms.  in  length  was  resected  without 
injury  to  the  mesentery.  The  edges  of  the  two  ends  of  the 
intestine  were  sewn  together  in  the  usual  way.  One  end  of  the 
resected  piece  of  intestine  was  closed  with  crossed  sutures  and 
replaced  ;  the  other  end,  left  open,  was  sewn  into  the  abdominal 
wound.  Although  Thiry  did  not  treat  the  wound  antiseptically, 
he  succeeded  in  preventing  peritonitis  in  a  few  cases,  and  in 
getting  the  wound  to  heal  quickly.  In  from  two  to  five  days 
the  animals  could  again  receive  food  into  their  shortened  intes- 
tine, and  remained  in  good  health  for  months.  Quincke  ^  has 
repeated  these  experiments  several  times ;  one  of  the  dogs  ex- 
perimented upon  lived  for  nine  months  after  the  operation,  and 
died  from  an  accident.  An  abundant  secretion  of  intestinal 
juice  was  brought  about  in  this  isolated  piece  of  intestine  by 
mechanical  and  chemical  stimulation,  especially  by  acids.  The 
juice  was  readily  obtained  for  examination  by  putting  in 
small  pieces  of  sponge,  which  were  removed  after  a  time  and 
squeezed  out. 

To  the  obvious  objection  that  a  secretion  thus  obtained  was 
not  normal  intestinal  juice,  Thiry  and  Quincke  replied  with  the 
following  arguments  :  1 .  The  microscopic  examination  of  the 
intestinal  wall  showed  no  changes  in  its  histological  structure 
as  a  whole,  or  in  Lieberkühn's  glands,  even  several  months 
after  the  operation.  2.  The  circulation  in  the  mesentery  and 
the  innervation  did  not  appear  to  be  disturbed;  the  reflex 
mechanism  was  maintained.  3.  Intestinal  parasites  continued 
to  live  in  the  isolated  piece  of  intestine :  a  Nematode  and  a  Tenia 

■*  Thiry,  Sitzungsber.  d.  Wiener  A/cad.,  vol.  1.  p.  77  :  1864. 
*  H.  Quincke,  Du  Bois'  Arch.,  p.  150 :  1868.     Compare  also  Leube,  Centralbl. 
f.  d.  med.  Wissensch.,  p.  289  :  1868. 

172 


INTESTINAL    JUICE    AND    BILE  173 

serrata,  tbe  latter  of  which  from  time  to  time  cast  off  ripe 
segments.  This  last  argument  is  rendered  convincing  by  the 
fact  that  these  creatures  exist  only  under  certain  conditions,  and 
that  most  kinds  of  intestinal  worms  live  only  in  certain  portions 
of  the  alimentary  canal  of  definite  animal  species. 

The  secretion  obtained  from  the  isolated  piece  of  intestine 
proved  to  have  no  action  on  any  of  the  three  main  groups  of 
organic  food-stuffs ;  fats  and  starch  flour  remained  unaltered. 
Of  the  proteids,  according  to  Thiry,  only  the  blood-fibrin  was 
dissolved,  but  no  other  kinds  of  proteid,  such  as  bits  of  meat 
or  coagulated  egg-albumin ;  gelatin  did  not  lose  its  power  of 
gelatinizing.  Quincke  could  not  even  confirm  the  action  of 
the  secretion  upon  fibrin  ;  he  found  the  intestinal  juice  quite 
inactive  on  all  food.  Lehmann  ^  also  came  to  the  same  con- 
clusions, when  he  examined  the  secretion  from  an  isolated  piece 
of  goat's  intestine.  Many  further  experiments  on  artificial 
digestion  have  been  carried  out  with  extracts  from  the  intes- 
tinal mucous  membrane  of  various  animals.  In  these  experi- 
ments there  was  either  no  action  to  be  observed  on  any  article 
of  diet,  or  a  very  slight  one  only  on  boiled  starch  flour,  when 
sugar  was  formed.  But  no  importance  should  be  attached  to 
the  last  results,  as  a  ferment  with  a  slow  action  upon  boiled 
starch  may  be  extracted  from  every  tissue. 

Lastly,  Demant  ^  has  more  recently  made  experiments  on 
the  action  of  the  intestinal  juice  in  human  beings.  Demant 
had  the  opportunity  of  collecting  pure  intestinal  juice  from  the 
lower  portion  of  intestine,  in  a  case  of  artificial  anus  after 
herniotomy,  which  occurred  in  Leube's  hospital-practice  in 
Erlangen.  A  part  of  the  intestine  bulged  out  like  a  sausage 
from  the  fistulous  opening  (of  which  there  were  two)  belonging 
to  the  lower  portion  of  the  intestine.  Usually  but  little  juice 
oozed  out  of  this  opening ;  the  supply  was  however  abundant 
after  meals,  and  could  be  collected  in  a  glass  beaker  which  was 
held  underneath  without  touching  the  intestinal  mucous  mem- 
brane. In  this  manner,  from  15  to  25  c.cms.  of  the  secretion 
were  obtained  in  the  course  of  one  day.  The  secretion  thus 
occurred  without  any  direct  chemical  or  mechanical  stimula- 

^  Karl  B.  Lehmann,  Pflüger's  Arch.,  vol.  xxxiii.  p.  180  :  1884.  Compare  also 
J.  Wenz,  Zeitschr.f.Biolog.,y(A.-s.-K.i\.T^.l:  1886;  Fr.  Pregl,  Pflüger's  ^rcA., 
vol.  Ixi.  p.  359 :  1895.  L.  Vella  obtained  different  results  on  repeating  Thiry's 
experiments  on  dogs  (Moleschott's  Unt.  zur  Naturlehre,  «fee,  vol.  xiii.  p.  40 : 
1881) ;  he  found  that  the  juice  acted  on  all  the  main  groups  of  food-stuffs.  This 
divergence  of  opinion  does  not  as  yet  admit  of  explanation. 

2  Bernh.  Demant,  Virchow's  Arch.,  vol.  Ixxv.  p.  419 :  1879.  Compare  the 
observation  of  a  similar  case  by  H.  Tubby  and  T.  D.  Manning,  Guy's  Hosp. 
Reports,  p.  271 :  1892. 


174  LECTURE   XII 

tion  of  the  raucous  membrane,  merely  from  the  normal  reflex 
irritation,  which  proceeded  from  the  upper  portions  of  the 
alimentary  canal.  It  is  therefore  probable  that  Demant  really 
obtained  the  normal  secretion,  and  not  an  inflammatory  tran- 
sudation of  mucous  membrane,  brought  about  by  abnormal 
irritation. 

The  intestinal  juice  of  man,  experimented  upon  by  Demant, 
appeared  to  produce  no  change  in  any  form  of  proteid,  nor  in 
fibrin  and  fats.  It  had  a  very  slight  action  on  boiled  starch, 
which  in  numerous  experiments  never  occurred  till  five  hours 
had  elapsed,  at  from  36°  to  38°  C.  No  trace  of  sugar  could 
be  detected  before  this  time  had  passed. 

If  the  intestinal  juice  has  no  action  upon  food,  of  what  im- 
portance is  it?  Will  not  its  chemical  composition  enlighten  us 
here?  Quincke  found  that  it  contained  remarkably  little  of 
any  organic  constituents ;  in  fact,  only  0.5  per  cent.,  which 
was  chiefly  proteid.  Thiry  found  somewhat  more.  Both  in- 
vestigators agree  that  the  amount  of  inorganic  salts  was  0.9 
per  cent.;  among  these  carbonate  of  soda  is  the  chief.  Both 
Thiry  and  Quincke  remarked  that  the  intestinal  juice  efiervesces 
on  the  addition  of  acids,  and  the  same  thing  has  been  noticed 
by  Demant  with  the  human  secretion. 

The  importance  of  the  intestinal  juice  lies  undoubtedly  in 
the  large  amount  of  carbonate  of  soda  it  contains.  Its  function 
is  to  neutralize  the  acids  of  the  intestinal  contents,  and  to 
emulsify  the  fats  with  the  surplus  carbonate  of  soda  (compare 
above,  p.  165).  It  has  to  supersaturate  not  only  the  hydro- 
chloric acid  of  the  gastric  juice,  but  also  the  acids,  sometimes 
existing  in  far  larger  quantities,  which  arise  from  the  butyric 
and  lactic  acid  fermentations.  The  rapidity  of  the  passage  of 
the  carbonate  of  soda  through  the  intestinal  wall  must  there- 
fore be  proportionate  to  the  acidity  of  the  intestinal  contents. 
For  as  soon  as  the  carbonate  of  soda  became  over-saturated, 
the  absorption  of  fat  would  necessarily  be  at  a  standstill  [as- 
suming that  emulsification  is  a  necessary  preliminary  to  ab- 
sorption] .  This  is  prevented  by  reflex  mechanism.  Thiry  and 
Quincke  observed  that,  on  stimulating  the  intestinal  mucous 
membrane  with  acids,  the  secretion  of  the  alkaline  intestinal 
juice  at  once  became  more  copious. 

To  this  interpretation,  that  the  emulsifying  and  absorption 
of  fats  is  brought  about  by  the  carbonate  of  soda  in  the  in- 
testinal juice,  the  objection  has  been  raised  that  the  absorption 
of  fats  begins  early  in  the  upper  part  of  the  intestine,  where 
the  reaction  of  the  intestinal  contents  is  always  acid.  Further, 
it  is  well  known  that  during  digestion  the  chyle-vessels  in  the 


INTESTINAL    JUICE    AND    BILE  175 

duodenum  become  opaque  and  white,  through  being  filled  with 
droplets  of  fat,  and  also  that  the  contents  of  the  entire  small 
intestine  as  far  as  the  cecum  occasionally  give  an  acid  reaction.^ 
To  this  I  would  reply,  that  it  is  not  the  reaction  of  the  internal 
part  of  the  food-mass  which  is  of  importance,  but  the  reaction 
of  its  surface  which  comes  in  contact  with  the  absorbing  intes- 
tinal wall.  That  this  latter  always  remains  alkaline  is  due  to 
the  above-mentioned  reflex  mechanism. 

It  appears  to  me  that  the  carbonate  of  soda  in  the  in- 
testinal juice  also  serves  another  purpose.  The  food  absorbs 
hydrochloric  acid  in  the  stomach ;  the  molecules  of  hydro- 
chloric acid  are  distributed  among  the  minutest  particles  of 
organic  food.  When  the  sodium  carbonate  neutralizes  the 
acid,  the  carbonic  acid  thus  liberated  effectually  separates  the 
minute  particles  of  the  organic  food  from  each  other.  The 
bulk  of  the  food  is  more  thoroughly  broken  up,  and  the 
digestive  ferments  gain  more  complete  and  easy  access  to  the 
individual  particles,  and  so  effect  the  rapid  solution  of  the  food 
in  the  intestine. 

In  conclusion,  I  must  not  omit  to  mention  that  another 
explanation  has  been  given  by  Hoppe-Seyler  of  the  action 
of  the  intestinal  juice,  which  is  opposed  to  mine.  Hoppe- 
Seyler's^  view  is  that  probably  no  special  intestinal  juice 
exists  as  a  secretion  of  Lieberkühn's  glands,  or  of  the  in- 
testinal mucous  membrane ;  at  any  rate,  he  sees  at  present  no 
proof  of  its  existence.  He  thinks  that,  the  quantitative  com- 
position of  the  supposed  intestinal  juice  being  identical  with 
that  of  the  blood-plasma  and  of  lymph,  we  cannot  regard  the 
fluid  obtained  from  Thiry's  intestinal  fistula  as  being  anything 
but  a  transudation  brought  about  by  abnormal  stimulation. 

In  reply,  I  would  merely  ask  how  we  are  to  explain  the 
fact  that  the  intestinal  contents,  which  give  an  acid  reaction 
in  the  upper  portion  of  the  small  intestine,  even  after  ad- 
mixture with  the  pancreatic  juice  and  with  bile,  are  nearly 
always  markedly  alkaline^  in  the  lower  portion  of  the  intes- 
tine, and  this  in  spite  of  the  incessant  lactic  and  butyric  acid 
fermentations. 

Hoppe-Seyler  teaches  that  the  recesses  of  the  intestines, 
designated  as  Lieberkühn's  glands,  serve  only  to  enlarge  the 
absorbent  intestinal  surface,  and  that  the  supposed  glandular 
epithelium  is  only  a  continuation  of  the  absorbent  epithelium 

1  Th.  Cash,  Du  Bois'  Arch.,  p.  323  :  1880. 

2  Hoppe-Seyler,  "  Physiologische  Chemie,"  pp.  270,  275 :  Berlin,  1881.  Com- 
pare Arthur  Hanau,  Zeitschr.  f.  Biolog.,  vol.  xxii.  p.  195 :  1886. 

ä  Gley  and  Lambling,  Rev.  biol.  du  Nord  de  la  France,  vol.  i.  :  1888. 


176  LECTURE    XII 

of  the  villi.  On  the  other  hand,  Heidenhain  ^  asserts  that  the 
epithelium  of  Lieberkiihn's  glands  differs  very  much  morpho- 
logicallv  from  the  epithelium  of  the  villi,  and  that,  as  the 
intestinal  contents  never  penetrate  into  Lieberkiihn's  glands, 
these  could  not  serve  for  absorption. 

The  BILE,  the  secretion  of  the  liver,  is  the  only  secretion 
poured  into  the  alimentary  canal  which  remains  for  our  con- 
sideration. The  secretion  of  bile  is  not  the  only  function  of 
the  liver.  This  is  soon  seen  by  comparing  the  size  of  the 
liver  and  the  small  amount  of  bile  produced  with  the  size  of 
other  glands  and  the  quantity  of  their  secretions.  The  human 
liver  weighs  from  1500  to  2000  grms.,  and  produces  in  twenty- 
four  hours  about  400  to  800  grms.  of  bile.^  The  parotid, 
which  weighs  only  from  24  to  30  grms.,  produces  in  the  same 
time  from  800  to  1000  grms.  of  secretion.  This  simple  fact 
shows  that  the  liver  probably  has  other  functions  to  perform. 
We  must  refer  our  readers  to  another  lecture  (Lecture  XXII.) 
for  an  account  of  the  numerous  and  complicated  chemical  proc- 
esses that  go  on  in  this  the  largest  of  all  the  glands,  and  of 
the  origin  of  the  bile  from  the  constituents  of  the  blood.  At 
present  we  have  only  to  do  with  the  secretion,  when  aifected, 
and  its  significance  in  intestinal  digestion. 

The  digestive  secretions  which  have  been  under  considera- 
tion do  not  contain  any  specific  constituents,  if  we  exclude  the 
ferments  which  we  are  unable  to  isolate.  So  far  as  our  knowl- 
edge goes,  they  consist  only  of  substances  which  are  distrib- 
uted all  over  the  body.  The  chief  solid  constituents  of  the 
bile,  on  the  other  hand,  are  found  to  consist  of  specific  organic 
compounds,  which  are  either  not  met  with  at  all  elsewhere  in 

1  Heidenhain,  Pfliiger's  Arch.,  vol.  xliii.  Sup.  p.  25 :  1888. 

2  For  the  method  of  establishing  a  biliary  fistula,  and  of  determining  the 
amount  of  bile  produced  in  twenty-four  hours,  see  Schwann,  Arch.  f.  Anat.  u, 
Physiol.,  p.  127:  1844;  Blondlot,  "Essai  sur  les  fonctions  du  foie,"  &c.  :  Paris, 
1846;  Bidder  and  Schmidt,  "Die  Verdauungssäfte  u.  der  Stofi"wechsel,"  p.  98; 
Leipzig  and  Mitau,  1852.  The  amount  of  bile  secreted  in  twenty-four  hours  in 
cases  of  men  with  biliary  fistulse,  was  estimated  by  J.  Ranke,  "Die  Blutverthei- 
lung  und  der  Thätigkeitswechsel  der  Organe,"  pp.  39,  145:  Leipzig,  1871;  v. 
Wittich,  Pflüger's  Arch.,  vol.  vi.  p.  181:  1872;  Westphalen,  Deutsch.  Arch.  f. 
Hin.  Sied.,  vol.  xi.  p.  588:  1873;  Gerald  F.  Yeo  and  E.  F.  Herroun,  Journ.  of 
Physiol.,  vol.  v.  p.  116 :  1884.  Copeman  and  Winston,  Journ.  Physiol.,  vol.  x. 
p.  213:  1889.  Mayo  Robson,  Proc.  Roy.  Soc,  vol.  xlvii.  p.  499:  1890;  Noel 
Baton  and  J.  M.  Balfour,  Rep.  Lab.  Roy.  Coll.  Phys.,  Edin.,  vol.  iii.  p.  191: 
1891.  The  amount  of  bile  in  twenty-four  hours  estimated  in  the  case  of  men 
with  biliary  fistula  is  certainly  too  small,  for  the  ductus  choledochus  was  open, 
and  a  part  of  the  bile  escaped  into  the  intestine.  With  animals  where  the  ductus 
choledochus  had  been  tied,  a  far  larger  amount  of  bile  was  obtained  proportionate 
to  their  weight.  Bidder  and  Schmidt  {loc.  cit.,  pp.  114-209)  found  from  13  to  29 
grms.  of  bile  in  tweuty-four  hours  to  every  kilogramme  of  weight,  in  the  case  of 
dogs;  with  cats,  an  average  of  14.5;  sheep,  25.4;  rabbits,  136.8. 


INTESTINAL    JUICE    AND    BILE  177 

the  animal  ^  body  or  only  in  traces.  We  will  therefore  proceed 
to  examine  these  compounds  more  closely. 

The  sodium  salts  of  two  complex  acids  form  the  chief 
constituents  of  the  bile  ;  glycocholic  acid  and  taurocholic  acid. 
The  former  of  these  acids  splits  up,  on  boiling  with  acids  and 
alkalies  as  well  as  when  acted  on  by  ferments  with  hydration, 
into  an  acid  free  from  nitrogen,  cholalic  acid,  and  into  a  sub- 
stance containing  nitrogen,  glycocoll.  The  taurochloric  acid 
splits  up,  by  the  same  means,  into  cholalic  acid,  and  into  a 
body  containing  both  nitrogen  and  sulphur,  taurin.^ 

In  spite  of  numerous  investigations,^  little  is  known  con- 
cerning the  constitution  of  cholalic  acid.  It  appears  that  the 
cholalic  acids  from  the  biliary  acids  of  various  animals  have  a 
different  composition,  although  possessing  similar  physical  and 
chemical  qualities.  The  formula  for  the  cholalic  acid  of  human 
bile  was  found  by  H.  Bayer  to  be  C^gH2g04,  while  that  of  the 
cholalic  acid  in  bullock's  bile  was  found  to  be  C„,II.„0,. 

24       40      5 

The  constitution  of  glycocoll  (glycin)  is  accurately  known. 
This  substance  can  be  synthetically  produced  from  monochlor- 
acetic  acid  and  ammonia,  and  is  therefore  the  same  as  amido- 
acetic  acid — CIl2(NIl2)COOH.  It  cannot  be  traced  in  a  free 
state  in  the  animal  body,  but  occurs  in  combination  with 
another  acid  than  cholalic  acid,  as  hippuric  acid.  We  shall 
soon  meet  with  it  again.  It  undoubtedly  originates  in  the 
animal  body  from  proteid.  It  can  be  artificially  prepared  from 
gelatin  by  boiling  with  dilute  acids,  and  gelatin  is  a  derivative 
of  proteid.  Being  produced  from  gelatin,  amido-acetic  acid 
received  the  name  glycocoll  (gelatin  sugar). 

Taurin  shows  its  origin  from  proteid  by  the  amount  of 
sulphur  it  contains.  Kolbe^  succeeded  in  producing  it  syn- 
thetically in  the  following  manner :    chlorethyl-sulphonate  of 

1  The  researches  of  Adolph  Strecker  in  Liebig's  Ännal.  (vol.  Ixv.  p.  130 : 
1848 ;  vol.  Ixvii.  p.  1 :  1848 ;  and  vol.  Ixx.  p.  149  :  1849)  form  the  groundwork 
of  all  subsequent  investigations  on  the  bile-acids.  Among  later  works,  I  must 
particularly  notice  a  series  of  experiments  carried  out  by  Heinrich  Bayer  in 
Hoppe-Seyler's  laboratory  at  Strassburg,  "  Ueber  die  Säuren  der  menschlichen 
Galle  "  {Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  293  :  1879).  A  summary  of  the 
earlier  work  done  in  this  field  is  also  given  here. 

^  Of  late  years  the  following  authors  have  worked  more  particularly  on  the 
subject  of  the  constitution  of  cholalic  acid  :  Tappeiner,  Zeitschr.  f.  Biolog.,  vol. 
xii.  p.  60:  1876;  Sitzungsher.  d.  Wiener  Akad.,  vol.  Ixxxvii.  part  ii.:  April, 
1878:  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  xii.  p.  1627  :  1879.  Compare  also  Lats- 
chinoff,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  xii.  p.  1518:  1879;  vol.  xiii.  pp.  1052, 
1911 :  1880 ;  vol.  xv.  p.  713 :  1882 ;  and  vol.  xviii.  p.  3039 :  1885 ;  as  well  as 
Hammarsten,  Jüova  Acta  Heg.  Soc.  Scient.  Upsala,  ser.  iii.:  1881;  Kutscheroff, 
Ber.  d.  deutsch,  chem.  Ges.,  vol.  xii.  p.  2325:  1879;  Cleve,  Compt.  rend.,  vol. 
xci.  p.  1073:  1880;  and  Oefversigt  af  Kongl  Vetenkaps.  Akad.  förh.,  No.  4, 
1882. 

'  Kolbe,  Ann.  d.  Chem.  u.  Pharm.,  vol.  cixii.  p.  33  :  1862. 

12 


178  LECTURE  xn 

silver,  CjH^ClSOgAg,  heated  at  100°  C.  in  sealed  tubes  with 
a  concentrated  solution  of  ammonia,  yields  silver  chlorid  and 
amido-ethyl  sulphonic  acid,  C2H^(NH2)S03H.  This  is  identical 
with  the  taurin  obtained  from  bile. 

The  comparative  amounts  of  taurocholic  and  glycocholic 
acids  vary  in  the  bile  of  different  mammals.  Glycocholic  acid 
predominates  in  bullock's  bile,  whereas  the  bile  of  Carnivora 
appears  to  contain  taurocholic  acid  only ;  at  any  rate,  this  is 
true  of  dog's  bile.^  Both  acids  are  found  in  human  bile  in 
very  varying  proportions,  although  glycocholic  acid  always 
predominates.^  Jacobsen  even  found  the  human  bile  in  one 
case  quite  free  from  sulphur,  and  in  three  other  cases  the 
sulphur  was  only  contained  as  a  sulphate.^ 

To  the  specific  constituents  of  bile  belong  also  the  bile 
pigments,  of  which  two  occur  in  the  bile  of  most  vertebrates ; 
one  red-brown,  bilirubin,  and  the  other  green,  biliverdin.  The 
first  is  readily  converted  into  the  second  by  oxidation.  Accord- 
ing to  the  preponderance  of  one  or  the  other,  and  according  to 
the  amount  of  each,  the  bile  is  of  a  yellow,  brown,  or  green 
color.  Both  coloring  matters  have  been  obtained  in  a  crystal- 
line form.  Bilirubin  has  the  composition  CjgHggN^Og ;  bili- 
verdin, CggH^gN^Og.*  They  are  closely  related  to  hematin 
and  hemoglobin,  and  we  shall  have  later  on  to  consider  their 
mode  of  origin  from  the  latter  in  greater  detail.  Both  color- 
ing matters  behave  like  acids ;  they  form  soluble  compounds 
with  metals  of  the  potassium  group,  insoluble  ones  with  those 
of  the  calcium  group.  Certain  gall-stones  owe  their  origin  to 
the  formation  of  these  insoluble  compounds  in  the  bile-ducts, 
under  conditions  which  have  not  yet  been  sufficiently  investi- 
gated. The  amount  of  coloring  matter  in  normal  bile  is  always 
very  small.  Stadelmann  ^  found,  for  instance,  an  average  of 
0.16  grm.  of  bilirubin  in  a  dog's  bile  in  twenty-four  hours. 

^^{Strecker,  Ann.  d.  Chem.  u.  Pharm.,  vol.  Ixx.  p.  178:  1849;  Hoppe-Seyler, 
Journ.  f.  prakt.  Chem.,  vol.  Ixxxix.  p.  283  :  1863. 

2  O.  Jacobsen,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  vi.  p.  1026 :  1873  ;  Trifa- 
nowsky,  Pfl tiger's  ^rcA.,  vol.  ix.,  p.  492:  1874;  Socoloff,  ibid.,  vol.  xii.  p.  54: 
1876 ;  Hammarsten,  Upsala  Läkareförenings  förhandlingar,  vol.  xiii.  p.  574 : 
1878;  Hoppe-Seyler,  "  Physiologische  Chemie,"  p.  301:  Berlin,  1881.  Gerald 
F.  Yeo  and  E.  F.  Herroun,  Journ.  of  Physiol.,  vol.  v.  p.  116:  1884. 

^  O.  .Jacobsen,  loc.  cit.,  p.  1028. 

*  Städeler,  Vierteljahr schrift  der  Züricher  naturf.  Ges.,  vol.  viii.  p.  1 :  1863  ; 
Ann.  d.  Chem.,  vol.  cxxxii.  p.  323:  1864;  Thudichura,  Journ.  f.  prakt.  Chem., 
vol.  civ.  p.  193 :  1868 ;  Maly,  Journ.  f.  prakt.  Chem.,  vol.  civ.  p.  28  :  1868 ;  or 
Sitzungsber.  d.  Wiener  A kad.  d.  Wissensch.,  yol.lvn.  part  ii. :  1868;  vol.  Ixx. 
part  iii.:  July,  1874;  vol.  Ixxii.  part  iii.:  October,  1875;  Ann.  d.  Chem.  u. 
Pharm.,  vol.  clxxxi.  p.  106:  1876. 

5  Ernst  Stadelmann,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xv.  p.  349  : 
1882. 


INTESTINAL    JUICE    AND    BILE  179 

These  pigments  do  not  appear  to  be  of  any  importance  in  in- 
testinal processes. 

Besides  these  specific  constituents,  the  bile  always  contains 
soaps,  lecithin,  and  Cholesterin  (see  Lecture  VI.).  The  quantity 
of  the  latter  is  considerable  ;  it  may  amount  to  2  J  per  cent.  It 
is  absolutely  insoluble  in  pure  water,  and  is  kept  dissolved  in 
the  bile  by  the  presence  of  soaps  and  bile-salts.  Under  patho- 
logical conditions,  of  which  nothing  definite  is  known,  Choles- 
terin separates  out  in  the  bile-ducts  and  forms  concretions, 
which  are  partly  pure  and  partly  mixed  with  bilirubin  and  car- 
bonate of  lime. 

Lastly,  mucin  belongs  to  the  constant  biliary  constituents. 
This  is  not  however  a  product  of  the  liver-cells,  but  of  the 
epithelial  cells  which  line  the  mucous  membrane  of  the  larger 
bile-ducts,  and  especially  of  the  gall-bladder.  The  latest  and 
most  complete  experiments  on  the  chemical  qualities  of  mucin 
have  been  carried  out  by  Landwehr.^  He  arrives  at  the  con- 
clusion that  mucin  is  a  compound  of  proteid  with  a  colloid 
carbohydrate,  which  latter  he  designates  "  animal  gum." 

[Of  late  years  the  mucins  and  mucoids  have  been  the 
subjects  of  several  careful  investigations,  the  true  starting- 
point  of  which  may  be  found  in  Schmiedeberg' s  masterly 
work^  on  the  composition  of  chondrin.  He  found  that 
chondrin  could  be  regarded  as  a  combination  of  gelatin  with 
a  conjugated  sulphuric  acid,  viz.,  chondretin-sulphuric  acid. 
Chondretin,  itself  not  a  reducing  substance,  could  be  converted 
by  boiling  with  dilute  acids  into  chondrosin,  which  has  a 
strongly  reducing  action  on  cupric  hydrate,  and  can  be  re- 
garded as  a  combination  of  glycosamine  (CgH^^O^NHj)  and 
glycuronic  acid  (COOH  •  C.HgO.).  In  chondrin  therefore  the 
group  which  gives  rise  to  the  reducing  substance  on  boiling 
with  acids,  contains  nitrogen.  This  is  also  the  case  with  the 
mucins  so  far  as  they  have  been  investigated.  Thus  Müller  ^ 
obtained  pure  glycosamine  hydrochlorate  from  mucin  of  the 
submaxillary  gland.  Leathes*  investigated  the  mucoid  of 
ovarial  cysts.  On  digestion  and  treatment  in  alkaline  solution 
with  copper  acetate,  a  gelatinous  precipitate  is  formed  which 
contains  the  reducing  groups  of  the  mucin.  The  results  of 
analysis  gave  the  formula  for  this  compound  Cj2H2iCuNOjg 
-f-  2HC1.     The  reducing  substance  therefore  has  probably  the 

^H.  A.  Landwehr,  Zeitschr.  f.physiol.  Chein.,  vol.  viii.  pp.  114,  122:  1883; 
and  vol.  ix.  p.  361 :  1885  ;  also  Centralbl.  f.  d.  med.  Wissensch.,  p.  369 :  1885. 

'  O.  Schmiedeberg,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxviii.  p.  355 :  1891. 

?  Müller,  Sitzungsher.  d.  Gesell,  s.  BeförderuTig  d.  ges.  Naturwissensch.  z. 
Marburg,  No.  6,  p.  117-126 :  1898. 

*  J.  B.  Leathes,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xliii.  p.  245  :  1899. 


180 


LECTURE    XII 


formula  Ci2H23NOi^ 


Leathes  gives  it  the  name  of  para-mu- 
cosin  and  regards  it  as  possibly  a  dihexosamine.] 

I  subjoin  the  following  analyses  as  instances  of  the  highly 
variable  quantitative  composition  of  human  bile  : — 


Obtained  fkom  the  Gall-Bladdek. 


From  a 
Fistula. 


Frerichs.* 

Gorup-Besanez.» 

Trifanowsky.» 

Hoppe- 

Seyler.* 

Jacob- 
sen.» 

IN   1000  PARTS  OF  BILE. 

2^ 
g  =>  si 

^x  5 
»  OS  a 

ja     -a 
bo  .  _r 
.Sr©  ja 

H  =«  g 

|P 

^|g 

OS  Ko 

0) 

.5  6   . 
1   c3  a) 

■£  O  c3 
-  C8  » 

1  q5 

a  Ca  a) 

Is" 

'^  3 

Collected  from 
gall-bladders 
in  post- 
mortems. 

.2 

TS 
O 

•Ö 
CS 

<s 

i 

I.           II. 

Water 

Solid  substances 

Mucin ^ 

Other  substances  insoluble  >■ 

in  alcohol J 

Sodium  taurocholate  .    .    .  \ 
Sodium  glycocholate  ...  J 
Sodium  palmitate  and  stea- 

rate        

860.0 
140.0 

26.6 
102.2 

3.2 

1.6 
6.5 

2.5 

2.0 

1.8 

0.2 
Trace 

859.2 
140.8 

29.8 
91.4 

9.2^ 

2.6J 

7.7 

2.0 
2.5 

2.8 

0.4 
Trace 

822.7 
177.3 

22.1 
107.9 

47.3 
10.8 

898.1 
101.9 

14.5 
56.5 

=1 

30.9/ 
6.3 

908.8 
91.2 
24.8 

4.6 

7.5 
21.0 

8.2 

5.2 

2.5 

910.8 
89.2 
13.0 

14.6 

19.3 
4.4 

16.3 

3.6 
0.2 
3.4 

12.9  ■» 

L4/ 

8.7 
30.3 

13.9 

7.3/ 

5.3 

3.5 

Trace 

977.4 
22.6 

2.3 

10.1 
1.4 

Sodium  oleate 

Fat        

0.10 

Lecithin       

Cholesterin 

Inorganic  salts 

KCl 

NaCl 

0.05 

0.56 

8.5 

0.28 

5.5 

Na^COa 

NajPO^ 

0.95 
1.3 

CaCOg 

Ca(PO,), ■> 

Mg^p^o, ; 

CaSO- 

FePO, 

0.37 
Trace 

Trace 

These  analyses  show  that  the  bile  obtained  from  the  gall- 
bladder is  much  more  concentrated  than  that  obtained  from 
the  fistula.  It  is  therefore  evident  that  an  absorption  of  water 
occurs  in  the  gall-bladder.     The  analyses    of  dog's  bile   by 


1  Frerichs,  Hannover  Ann.,  Jahrg.  v.  Heft  i.:  1845. 

2  Von  Gorup-Besanez,  Prager  Vierteljahr  sehr.,  vol.  iii.  p.  86:  1851. 
^  Trifanowsky,  Pfliiger's  Arch.,  vol.  ix.  p.  492 :  1874. 

*  Hoppe-Seyler,  "  Physiologische  Chemie,"  p.  301 :  Berlin,  1881. 

"O.  Jacobsen,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  vi.  p.  1026  :  1873.  The  bile 
was  taken,  at  intervals  of  a  few  days,  from  a  biliary  fistula  open  for  several 
weeks,  the  patient  being  a  powerful  man. 


INTESTINAL    JUICE    AND    BILE 


181 


Hoppe-Seyler/  in  which  he  compared  the  bile  found  in  the 
bladder,  and  collected  while  the  animal  was  fasting,  with  that 
from  a  temporary  fistula  on  the  same  animal,  are  in  accordance 
with  this  observation. 


Bile  from  bladder. 

Bile  from  fistula. 

I. 

II. 

I. 

n. 

Mucin 

0.454 

0.245 

0.053 

0.170 

Alkaline  taurocholate 

11.959 
0.449 

12.602 
0.133 

3.460 
0.074 

3.402 

Cholesterin 

0.049 

Lecithin 

2.692 

0.930 

0.118 

0.121 

Fats                

2.841 

0.083 

0.335 

0.239 

Soaps      ...               

3.155 

0.104 

0.127 

0.110 

Other  organic  substances,  not  soluble  in  alcohol 

0.973 

0.274 

0.442 

0.543 

Inorganic  substances,  not  dissolved  in  alcohol 

0.199 

— 

0.408 

— 

In  the  above  :  KoSOi      • 

0.004 
0.050 

z 

0.022 
0.046 



NajSO^ 

— . 

NaC12 

0.015 
0.005 
0.080 

— 

0.185 
0.056 
0.039 



NajCOg 



Ca,2(P0). 



FePOi         

0.017 

— 

0.021 

— 

CaCOg 

0.019 
0.009 

— 

0.030 
0.009 



MgO 

— 

More  recently  Hammarsten^  has  had  the  opportunity  of 
analyzing  a  number  of  specimens  of  human  bile  obtained  from 
the  gall-bladder  as  well  as  from  fistulse. 


Solids 

Water  .    .    . 

Mucin  and  pigment 
Bile-salts 

Taurocholate  .    .    . 
Glycocholate 
Fatty  acids      .    .    . 
Cholesterin      .    .    . 
Lecithin  .    . 

Fat 

Soluble  salts     .    . 
Insoluble  salts     .    . 


Bile  from  fistula. 


1.63 
98.37 
0.36 
0.26 
0.06 
0.20 
0.04 
0.05 

0.02 

0.85 
0.04 


2 

3 

4 

5 

2.06 

2.52 

2.84 

2.45 

97.94 

97.48 

97.16 

97.55 

0.28 

0.53 

0.91 

0.88 

0.85 

0.93 

0.81 

0.56 

0.11 

0.30 

0.05 

— 

0.74 

0.63 

0.76 

— 

— 

0.12 

0.02 

— 

0.08 

0.06 

0.10 

0.06 

0.03 

0.02 

0.05 

0.08 

0.02 

0.80 

0.81 

0.81 

0.89 

0.02 

0.03 

0.04 

0.03 

3.53 
96.47 
0.43 
1.82 
0.21 
1.61 
0.14 
0.16 
0.06 
0.10 
0.68 
0.05 


2.54 
97.46 
0.52 
0.90 
0.22 
0.69 
0.10 
0.15 
0.07 
0.06 
0.73 
0.02 


From  gall-bladder. 


17.03 
82.97 
4.19 
9.70 
2.74 
6.96 
1.12 
0.99 
0.22 
0.19 
0.29 
0.22 


16.02 
83.98 
4.44 
8.72 
1.93 
6.79 
1.06 
0.87 
0.14 
0.15 
0.30 
0.24 


1893. 


^  Hoppe-Seyler,  loc.  cit.,  p.  302. 

2  The  greater  part  of  the  NaCl  was  dissolved  by  alcohol,  and  not  estimated. 

^  Olf  Hammarsten,  J}fova  Acta  Beg.  Societat.  Scient.  JJpsal.,  ser.  iii.,  vol.  16  ; 


182  LECTURE   XII 

Having  ascertained  the  composition  of  the  bile,  we  must 
now  consider  its  uses.  There  has  been  much  dispute  on  this 
point.  Some  have  even  denied  that  it  is  of  any  essential  use 
whatever,  and  have  regarded  it  simply  as  an  excretion  like  the 
urine.  The  fact  that  the  bile  is  poured  into  the  commencement 
of  the  intestine,  into  the  duodendum,  is  opposed  to  this  view. 
If  the  bile  were  an  excretion,  we  should  expect  the  bile-duct  to 
open  into  the  lower  end  of  the  rectum,  just  as  the  ureter  opens 
into  the  cloaca  in  the  lower  vertebrates.  It  is  impossible  not  to 
believe  that  bile,  in  its  long  passage  through  the  intestines,  must 
have  some  serious  duties  to  perform. 

The  constituents  of  the  bile  are,  to  a  very  large  extent,  re- 
absorbed by  the  intestine — a  fact  which  is  strongly  opposed  to 
its  being  an  excretion.  The  bile  acids,  which  are  the  most  im- 
portant constituents,  are  split  up  by  the  ferments  contained  in 
the  intestine  into  cholalic  acid  and  taurin  or  glycocoll ;  the  lat- 
ter, a  very  easily  soluble  substance,  disappears  entirely.^  Of 
the  cholalic  acid  only  a  very  small  part  is  excreted  in  the  feces. 
Concerning  the  ultimate  fate  of  the  taurin  nothing  is  known 
with  certainty.^ 

If  the  bile  were  an  excretion  like  urine,  we  should  expect 
to  find  the  quantity  of  nitrogen  and  sulphur  in  the  bile  varying 
proportionately  with  the  amount  of  proteid  decomposed  in  the 
body.  As  a  matter  of  fact,  this  is  not  the  case.  We  know 
from  the  researches  of  Kunkel  ^  and  Spiro,"*  conducted  on  dogs 
with  biliary  fistulse,  that  only  a  small  part  of  the  sulphur  and 
nitrogen  resulting  from  proteid  metabolism  appears  in  the  bile, 
and  that  it  is  but  very  slightly  increased  by  a  larger  supply  of 
food.  When  the  amount  of  proteid  allowed  the  dog  was  mul- 
tiplied eightfold  the  nitrogen  and  sulphur  of  the  bile  were  only 
doubled. 

All  these  facts  speak  in  favor  of  the  view  that  the  bile 
must  be  regarded  as  a  secretion,  like  the  other  secretions  which 
are  poured  into  the  alimentary  canal  and  exert  a  manifestly  im- 
portant influence  in  the  process  of  digestion.  But  the  follow- 
ing fact  shows  that  the  bile  occupies  a  peculiar  position.  The 
secretion  of  the  bile  begins  in  the  third  month  of  embryonic 

■^  On  the  further  fate  of  the  glycocoll,  see  Lecture  XIX. 

2  The  most  extended  researches  on  taurin  have  been  made  by  Salkowski,  Ber. 
d.  deutsch,  ehem.  Ges.,  vol.  v.  Heft,  xiii.:  1872;  vol.  vi.  pp.  744,  1191, 1312:  1873; 
Virchow's  Arch.,  vol.  Iviii.  p.  460:  1873. 

3  Kunkel,  "Unt.  über  den  Stoffwechsel  in  der  Leber":  Würzburg,  1875: 
Ber.  d.  sack.  Ges.  d.  Wissensch.:  November,  1875 ;  Pflüger's  Arch.,  vol.  xiv.  p. 
344:  1876. 

*  Spiro,  Du  Bois'  Arch.,  Suppl.,  p.  50:  1880  (from  Ludwig's  laboratory  in 
Leipzig). 


INTESTINAL    JUICE    AND    BILE  183 

life ;  the  activity  of  all  the  other  glands  which  empty  their 
secretions  into  the  alimentary  canal  does  not  commence  till  after 
birth,  when  food  is  first  taken. ^  Moreover  the  observation  of 
Lukjanow^  that  the  secretion  of  bile  in  guinea-pigs  is  only 
slightly  diminished  during  starvation  is  against  the  conception 
of  bile  as  a  digestive  secretion. 

It  has  been  attempted  to  decide  the  question  as  to  the  func- 
tion of  the  bile  in  intestinal  processes  by  watching  the  digestive 
disturbances  which  occur  when  the  bile  is  withdrawn.^  It 
appears  that  dogs  with  a  biliary  fistula  digest  proteid  and 
carbohydrates  as  completely  as  healthy  dogs.  They  can  be 
adequately  fed  on  lean  meat  and  bread.  Fat  is  the  only 
food-stuff  that  they  cannot  entirely  digest,  and  a  considerable 
part  of  it — more  than  half  if  much  be  eaten — reappears  in 
the  feces,  which  for  this  reason  are  of  a  light  gray  or  white 
color.  This  is  not  owing  to  the  want  of  the  bile  pigments, 
as  was  originally  thought.  The  black  color  of  the  normal 
feces  after  meat  diet  is  not  caused  by  the  bile  pigments,  but 
by  hematin  and  sulphid  of  iron.  If  the  light  gray  feces  of 
an  animal  with  a  biliary  fistula  or  of  a  jaundiced  person  be 
extracted  with  ether,  which  dissolves  the  fat,  the  dark  color  is 
again  evident.  In  consequence  of  the  imperfect  absorption  of 
the  fat,  the  other  food-substances  cannot  be  completely  digested. 
The  fat  encloses  the  proteids,  which  become  decomposed  by 
the  putrefactive  organisms  of  the  intestine.  This  explains  the 
putrefactive  smell  of  the  feces  and  the  intestinal  gases  in 
dogs  with  a  biliary  fistula.  The  breath  of  the  animals  be- 
comes fetid.  These  symptoms  are  all  absent  when  a  diet  with- 
out fat  is  given. 

Many  of  the  dogs  with  a  biliary  fistula  that  have  been 
under  observation  became  very  thin,  and  a  few  died  with  every 
symptom  of  starvation.  This  is  readily  comprehensible  if  we 
consider  how  high    the   heat-equivalent   of  fats    is,  and   how 

^Zweifel,  "  Unt.  über  den  Verdauungsapparat  des  Neugeborenen"  :  Berlin, 
1874.  An  account  of  the  comprehensive  literature  on  the  action  of  the  digestive 
glands  in  embryonic  life  is  to  be  found  in  W.  Preyer's  "  Specielle  Physiol,  des 
Embryo,"  p.  306:  Leipzig,  1885. 

2  S.  M.  Lukjanow,  Zeitschr,  f.  physiolog.  Chem.,  vol.  xvi.  p.  87:  1891. 

3  Schwann,  Arch.  /.  Anat.  u.  Physiol.,  p.  127 :  1844 ;  Blondlot,  "  Essai  sur  les 
fonctions  du  foie  et  de  ses  annexes  "  :  Paris,  1846  ;  Bidder  and  Schmidt,  loc.  cit.; 
Köllicker  and  Müller,  Verh.  d.  phys.  med.  Ges.  zu  Würzburg,  vol.  v.  p.  232  :  1854; 
vol.  vi. :  1855 ;  Arnold,  "  Zur  Physiol,  der  Galle,"  Denkschrift  für  Tiedemann  : 
Mannheim,  1854 ;  and  "  Die  physiol.  Anstalt  der  Universität  Heidelberg  "  :  1858 ; 
C.  Voit,  Beitr.  zur  Biolog.  Festgabe  Th.  Bischoff  zum  Doctorjubiläum,  Stutt- 
gart, p.  104;  F.  Röhmann,  Pflüger's  Arch.,  vol.  xxix.  p.  509:  1882.  The 
observations  on  icteric  patients  are  in  complete  harmony  with  those  on  dogs  with 
biliary  fistulse.  In  this  connection  see  Fr.  Müller,  Sitzungsber.  der  physikal.  med. 
Ges.  zu  Würzburg,  No.  7  :  1885. 


184  LECTURE    XII 

difficult  it  is  to  replace  this  potent  source  of  energy  by  other 
articles  of  food.  It  is  necessary  for  this  purpose  to  consume 
very  large  quantities  of  proteid  and  carbohydrates,  and  the 
digestion  of  these  substances  is  disturbed  by  the  presence  of  the 
unabsorbed  fat.  Therefore  only  those  dogs  kept  their  weight 
which  were  fed  on  food  as  far  as  possible  free  from  fat,  and  that 
in  very  large  quantities. 

It  is  therefore  an  undoubted  fact  that  bile  aids  iu  the  absorp- 
tion of  fat.  This  power  is  partly  explamed  by  the  emulsi- 
fying action  on  fats  already  mentioned  (p.  164),  which  the 
bile  possesses  in  common  with  the  pancreatic  and  intestinal 
juices.  In  agreement  with  this  is  the  fact  that  the  with- 
drawal of  the  bile  only  diminishes  the  absorption  of  fat,  and 
does  not  completely  stop  it.  Possibly  it  is  not  only  the 
emulsifying  action  of  the  bile  which  assists  in  the  absorption 
of  fat.  Wistinghausen  ^  showed  that,  when  oil  is  separated 
from  a  watery  fluid  containing  bile  in  solution  by  an  animal 
membrane  soaked  in  bile,  it  filters  through  without  any  pres- 
sure, whereas  it  can  only  be  made  to  pass  through  a  membrane 
soaked  m  water  by  the  employment  of  high  pressure.  But  the 
intestinal  wall  does  not  behave  like  a  dead  membrane.  Than- 
hoifer,-  who  first  observed  in  the  frog's  intestine  the  active  func- 
tions of  the  epithelial  cells  iu  the  absorption  of  fats,  also 
mentions  that  the  movement  of  the  protoplasmic  processes 
becomes  more  active  when  the  epithelial  cells  are  moistened 
with  bile. 

The  process  of  fat  absorption  is  however  by  no  means  ex- 
plained by  the  facts  we  have  discussed.  The  emulsion  of  the 
fat  by  the  alkaline  constituents  of  the  intestinal  pancreatic 
juices  and  of  the  bile  will  not  serve  alone  to  explain  the 
process.  The  pancreatic  secretion  and  bile  have  still  an- 
other part  to  play  in  the  process.  We  know  for  certain  that 
the  absorption  can  only  take  place  by  the  cooperation  of  both 
juices.  In  the  rabbit  the  pancreatic  duct  opens  into  the 
duodenum  10  cms.  lower  down  than  the  bile  duct.  After 
the  administration  of  fatty  food  the  lacteals  may  be  seen  to  be 
transparent  in  the  interval  between  these  two  openings,  and 
only  assume  the  milky  appearance  below  the  orifice  of  the 
pancreatic  duct.  Dastre  experimentally  changed  the  relative 
position  of  the  two  ducts.  He  ligatured  the  common  bile  duct 
and  made  a  fresh  opening  for  the  bile  by  a  commnnication 

^  Wistinghausen,  "  Experimenta  quaedam  endosmotica  de  bills  in  absorptione 
adipum  neutralium  partibus,"  Dissert.:  Dorpat,  1851.  A  translation  of  this 
dissertation  was  publisiied  by  J.  Steiner  in  Du  Bois'  Arch.,  p.  137  :  1873. 

2  Ludwig  von  Thanhoffer,  Pfliiger's  Arch.,  vol.  viii.  p.     40  1874. 


INTESTINAL    JUICE    AND    BILE  185 

between  the  gall-bladder  and  the  small  intestine  some  distance 
below  the  opening  of  the  pancreatic  duct.  After  this  procedure 
the  milky  appearance  of  the  lacteals  first  became  evident  below 
the  point  of  entry  of  the  bile.  We  must  therefore  conclude 
that  neither  the  bile  by  itself,  nor  the  pancreatic  juice  by  itself, 
can  effect  any  considerable  absorption  of  fat. 

[It  seems  most  probable  that  the  absorption  of  fat  resembles 
that  of  the  other  food-stuffs  in  that  it  takes  place  in  a  state  of 
solution.  The  pancreatic  juice  first  causes  a  splitting  of  the  fat 
into  fatty  acid  and  glycerin.  If  the  reaction  is  alkaline  the 
fatty  acid  may  combine  with  the  alkalies  to  form  soaps.  What- 
ever be  the  reaction  of  the  intestinal  contents,  however,  the  fat 
is  absorbed  either  as  a  solution  of  fatty  acids  in  the  bile-salts  or 
as  a  solution  of  soaps  in  the  bile.  The  cooperation  of  both 
juices  is  therefore  necessary :  the  pancreatic  juice  to  split  the 
fats,  the  bile  to  dissolve  the  products  of  this  fermentative 
action  and  carry  them  into  solution  into  the  epithelial  cells  of 
the  intestine,  where  the  fatty  acids  and  soaps  are  resynthesized 
with  glycerin  to  form  neutral  fats,  while  the  bile-salts  are 
carried  by  the  portal  blood  to  the  liver  to  be  turned  out  again 
into  the  beginning  of  the  intestinal  tract  and  serve  as  a  vehicle 
for  a  still  further  quantity  of  fat.] 

No  action  of  bile  on  proteid  could  be  demonstrated  in 
experiments  on  artificial  digestion.  A  slight  diastatic  effect 
was  indeed  noticed,  but,  for  the  reasons  above  stated  no  weight 
can  be  attached  to  this  observation.  Bile  must  however  have 
some  other  functions  besides  that  of  assisting  in  fat  absorption, 
since  the  quantity  of  bile  secreted  by  herbivora,  whose  diet  is 
poor  in  fat,  is  much  greater  than  that  formed  by  Carnivora  with 
their  rich  fatty  diet. 

An  antiseptic  property  has  also  been  ascribed  to  bile  on 
account  of  the  putrefactive  phenomena,  mentioned  above,  which 
appeared  in  the  intestine  of  animals  with  a  biliary  fistula. 
But,  as  was  then  shown,  these  signs  of  putrefaction  are  capable 
of  another  explanation ;  they  depend  only  indirectly  upon  the 
absence  of  the  bile.  For  as  the  bile  cannot  protect  even  itself 
from  putrefaction,  it  is  evident  that  it  can  have  but  little  anti- 
septic power.  Any  one  who  has  experimented  with  bile  knows 
that  it  emits  a  strong  putrefactive  odor  after  a  few  days,  even 
when  kept  at  the  temperature  of  a  dwelling-room.  The 
doctrine  of  the  antiseptic  properties  of  bile  has  recently  again 
found  supporters  in  Maly  and  Emich.^  They  affirm  that  the 
bile  acids,  and  especially  taurocholic  acid,  prevent  the  develop- 
ment of  putrefactive  organisms,  and  that  taurocholic  acid  in 

1  Maly  and  Fr.  Emich,  Blonatshefte  f.  Chem.,  vol.  iv.  p.  89  :  1883. 


186  LECTUKE    XII 

many  cases  is  nearly  as  powerful  as  salicylic  acid  and  phenol. 
This  view  has  been  confirmed  by  Lindberger*  as  well  as  by 
Gley  and  Lambling.^  But  still  it  is  only  the  free  bile  acids  that 
hinder  putrefaction,  and  not  the  salts.  This  explains  why  bile 
itself  which  is  alkaline  or  neutral,  rapidly  decomposes  outside 
the  body,  whereas  the  bile  acids  can  develop  their  antiseptic 
properties  only  in  the  upper  portion  of  the  small  intestine, 
where  an  acid  reaction  prevails. 

'  V.  Lindberger,  Bulletin  de  la  Soc.  imp.  des  naturalistes  de  Moscou :  1884. 
*  Gley  and  Lambling,  Rev.  hiol.  du  Nord  de  la  France,  vol.  i.:  1888. 


LECTURE  XIII 

THE    PATHS    OF    ABSORPTION,    AND    THE   IMMEDIATE  DESTINA- 
TION   OF    THE    ABSORBED    FOOD-STUFFS 

We  have  hitherto  been  considering  the  fate  of  the  food-sub- 
stances in  the  intestine  and  the  preparation  they  undergo 
previous  to  absorption.  Our  attention  must  now  be  given  to 
the  paths  which  the  food-stuflPs  follow  in  undergoing  absorp- 
tion. 

The  investigations  of  Ludwig  and  of  his  pupils  Röhrig/ 
Zawilski/  von  Mering,^  and  Schmidt-Mülheim/  have  thrown  an 
unexpected  light  on  this  subject.  Till  modern  times  it  was 
commonly  assumed  that  the  main  stream  of  nutriment  passed 
from  the  intestine  through  the  thoracic  duct.  But  Ludwig's 
experiments  have  shown  that  it  is  only  the  fats  which  take  this 
path.  The  whole  stream  of  watery  solutions,  carbohydrates, 
proteids,  salts,  etc.,  proceeds  from  the  intestine  to  the  heart, 
through  the  portal  system  and  the  liver.  The  watery  solutions 
penetrate  the  walls  of  the  capillaries  which  form  a  network  on 
the  internal  surface  of  the  intestine,  and  enter  the  blood  direct. 
The  droplets  of  fat  alone  are  brought  to  the  commencement  of 
the  lacteals  by  the  active  movements  of  the  epithelial  cells. 

If,  in  a  living  dog,  the  spot  where  the  thoracic  duct  opens 
into  the  jugular  vein  ^  be  laid  bare,  a  cannula  may  be  intro- 
duced into  the  duct,  and  the  amount  of  chyle  that  flows  out  in 
a  given  time  estimated.  The  astonishing  fact  was  discovered 
that  the  amount  was  no  greater  during  digestion  than  in  a 
fasting  animal.^  The  sole  difference  was  that  the  fluid  was 
transparent  in  the  case  of  fasting  animals,  whereas  after  food 

1  A.  Röhrig,  Ber.  d.  sacks.  Ges.  d.  Wissensch.  Math.  phys.  Classe,  vol.xxvi.: 
1874. 

2  Zawilski,  Arbeiten  aus  der  physiol.  Anstalt  zu  Leipzig,  p.  147 :  1876. 
ä  von  Mering,  Du  Bois'  Arch.,  p.  379  :  1877. 

*A.  Schmidt-Mülheim,  ibid.,  p.  549. 

^  For  the  mode  of  operation  and  the  precautions  adopted  during  the  sub- 
sequent post-mortem,  see  A.  Röhrig,  loc.  cit.,  pp.  12,  13  ;  and  Schmidt- Mülheim, 
loc.  cit.,  pp.  559-561. 

«  Zawilski,  loc.  cit.,  pp.  161,  162. 

187 


188  LECTURE    XIII 

it  was  white  and  opaque  from  the  presence  of  min  ate  particles 
of  fat. 

On  the  other  hand,  the  amount  of  sugar  in  the  chyle  was 
not  found  to  be  greater  during  the  digestion  of  starch  and 
sugar  than  in  the  fasting  animal — 0.1  to  0.2  per  cent.^  The 
amount  of  sugar  in  the  chyle  was  always  the  same  as  in  the 
lymph  from  the  cervical  lymphatic  trunks,  and  in  the  serum  ^ 
of  the  arterial  blood.  The  sugar  of  the  chyle  had  therefore 
passed  through  the  walls  of  the  intestinal  capillaries  into  the 
chyle-vessels  along  with  the  blood-plasma.  From  the  intestine 
no  sugar  had  got  through  into  the  chyle. 

Three  hundred  and  fifty  cubic  centimeters  of  chyle,  con- 
taining only  0.45  grm.  of  sugar,  flowed  during  the  space  of 
four  and  a  half  hours  from  the  thoracic  duct  of  a  dog,  after 
it  had  eaten  100  grms.  of  grape-sugar  and  100  grms.  of 
starch.^ 

We  must  therefore  conclude  that  the  sugar  reaches  the 
capillaries  and  the  portal  system  direct  from  the  intestine. 
But  uow  we  see  that  the  amount  of  sugar  in  the  blood  is  not 
increased  even  after  a  meal  rich  in  carbohydrates.  An  adult 
man  has  about  5  liters  of  blood,  and  in  each  liter  0.5  to  1.5 
grms.  sugar,  rarely  more  than  2  grms.,  so  that  the  whole  blood 
contains  at  most  10  grms.  This  amount  remains  the  same  in  a 
hungry  as  in  a  well-fed  animal.  During  the  few  hours  elapsing 
after  a  meal  rich  in  carbohydrates,  as  much  as  400  grms.  of 
sugar  may  pass  into  the  blood.  What  becomes  of  this  sugar  ? 
It  cannot  always  be  employed  as  a  source  of  energy  as  quickly 
as  it  is  absorbed,  especially  when  the  body  is  at  rest  and  does 
not  need  to  produce  much  heat.  The  sugar  must  therefore  be 
stored  up  somewhere  and  in  some  form  or  other,  in  order  that 
it  may  serve  as  a  store  of  potential  energy  for  later  utiliza- 
tion. 

We  naturally  think  first  of  glycogen,  the  colloid  carbo- 
hydrate stored  up  in  the  liver  and  muscles,  which  we  shall  have 
to  deal  with  more  fully  later  on.  We  know  that  this  store  of 
glycogen  gradually  disappears  in  hunger  and  during  work 
(compare  Lectures  XXII.  and  XXIII.),  and  rapidly  increases 
in  amount  after  ingestion  of  carbohydrates. 

But  the  large  quantities  of  sugar  which  are  frequently 
absorbed  from  the  intestine  into  the  blood  within  a  short  space 
of  time  cannot  possibly  be  all  stored  up  as  glycogen.     The 

1  von  Mering,  loc.  cit.,  pp.  382-384,  398. 

2  The  blood-corpuscles  contain  no  sugar,  or  only  a  trace  of  it  (see  von  Mering, 
loc.  cit.,  p.  382  ;  and  A.  M.  Bleile,  Du  Bois'  Arch.,  p.  62  :  1879). 

*  von  Mering,  loc.  cit.,  p.  398. 


THE    PATHS    OF    ABSORPTION  189 

total  amount  of  glycogen  in  the  liver  in  man  never  exceeds  150 
grms.,  and  a  similar  quantity  might  be  stored  up  in  the  whole 
mass  of  muscles.  This  store  however  is  by  no  means  used  up 
at  the  time  when  fresh  carbohydrates  are  taken  into  the  body, 
and  disappears  only  after  several  weeks'  starvation.  If  there- 
fore 400  grms.  of  sugar  are  poured  into  the  blood  within  a  few 
hours  after  a  carbohydrate  meal,  it  is  evident  that  only  a  small 
proportion  of  it  can  be  laid  down  as  glycogen  ;  and  we  must 
assume  that  the  greater  part  of  it  is  converted  into  fat.  In  this 
form  very  large  quantities  of  food  can  be  stored  up  in  the  con- 
nective tissue  of  all  the  organs,  and  we  shall  see  later  (Lecture 
XXIV.)  that  carbohydrates  are,  as  a  matter  of  fact,  converted 
into  fat  in  our  tissues. 

The  present  state  of  our  knowledge  enables  us  therefore  to 
form  the  following  conception  concerning  the  fate  of  the  sugar 
that  is  taken  into  our  body: — Sugar  is  an  important  food-stuff — 
an  important  source  of  energy  for  the  muscles  and  probably  for 
all  contractile  tissues.  Hence  provision  has  been  made  in  our 
bodies  for  a  certain  percentage  of  it  to  be  constantly  present 
in  the  blood  which  circulates  through  all  the  tissues.  If  its 
amount  in  the  blood  increases  to  more  than  3  per  mille,  excre- 
tion of  sugar  takes  place  through  the  kidneys  (compare  Lecture 
XXVI.).  This  loss  of  precious  food-stuff  is  prevented  by  the 
fact  that  the  liver  and  muscles  at  once  store  up  as  glycogen  any 
excess  above  the  normal  resulting  from  a  rapid  absorption.  If 
the  consumption  be  increased  by  work  and  heat  production  so 
as  to  diminish  the  normal  percentage  of  sugar  in  the  blood,  the 
muscles  and  liver  at  once  give  back  a  portion  of  the  glycogen 
to  the  blood  in  the  form  of  sugar.  If  the  store  of  glycogen 
is  insufficient,  fat  is  converted  into  sugar  and  transferred  to 
the  blood.  In  a  subsequent  lecture  (Lecture  XXII.)  we  shall 
deal  with  the  grounds  for  assuming  that  such  a  conversion 
takes  place.  We  know  for  a  fact  that,  after  long-continued 
hunger,  when  the  store  of  glycogen  has  quite  disappeared,  the 
percentage  of  sugar  in  the  blood  remains  constant.  Sugar  is 
also  in  all  probability  formed  from  proteid  (compare  Lecture 
XXIL). 

The  question  now  arises  as  to  the  reason  why  the  amount  of 
FAT  in  the  blood  is  not  regulated  in  the  same  way  ?  The  stream 
of  fat  being  poured  freely  into  the  innominate  vein  goes  almost 
directly  to  the  heart.  May  not  this  be  fraught  with  danger  ? 
The  blood  is  in  fact  frequently  flooded  by  the  stream  of  fat. 
If  blood,  which  has  been  taken  from  a  dog  a  few  hours  after  a 
meal  containing  an  abundance  of  fat,  be  defibrinated,  the  serum 
separated  out  after  the  blood-corpuscles   have  sunk,  appears 


190  LECTURE  xni 

as  white  as  milk,  occasionally  with  a  regular  cream-like  layer 
on  the  top.  This  abundance  of  fat  in  the  blood  is  quite  harm- 
less, because  the  fat-droplets  are  so  small  that  they  circulate 
without  hindrance  through  the  capillaries.  The  fat  gradually 
disappears  from  the  blood,  for  the  obvious  reason  that  it  travels 
through  the  walls  of  the  capillaries,  and  becomes  stored  up  in 
the  cells  of  the  connective  tissue  (compare  Lecture  XXIV.). 
It  is  impossible  for  the  fat  to  be  decomposed  within  the  vessels, 
since,  as  we  know,  processes  of  oxidation  never  take  place  in 
the  blood  (see  Lecture  XVIL). 

The  fat  which  reaches  the  blood  under  abnormal  conditions 
behaves  very  diiferently.  In  comminuted  fractures  of  the 
bones  causing  a  destruction  of  the  marrow  which  contains  a 
great  deal  of  fat,  or  when  the  soft  parts  containing  much  fat 
are  damaged  in  any  way,  fat-droplets  are  often  drawn  into  the 
lymph-vessels  and  carried  with  the  lymph  into  the  blood.  If 
the  amount  of  fat  is  considerable,  the  larger  particles  of  fat 
block  the  pulmonary  capillaries  over  wide  areas,  edema  of  the 
lungs  is  set  up,  and  it  occasionally  happens  that  the  patient  dies 
with  all  the  signs  of  increasing  dyspnea.  The  fat  may  in  these 
cases  seek  a  way  out  through  the  kidneys,  and  the  occurrence  of 
droplets  of  fat  in  the  urine  after  fractures  of  bone  is  not  at  all 
uncommon. 

The  question  might  now  be  raised  as  to  why  this  fat, 
which  reaches  the  blood  from  the  tissues,  is  not  emulsified 
into  minute  droplets,  seeing  that  the  blood  contains  sodium 
carbonate  and  other  basic  alkaline  salts.  The  answer  is 
to  be  found  in  the  fact  already  mentioned  (p.  164),  that 
sodium  carbonate  can  only  emulsify  fat  which  has  a  little 
free  fatty  acid  mixed  with  it,  and  not  neutral  glycerids  such 
as  fresh  fats  are.  But  no  fat  can  be  fresher  than  when  it 
comes  straight  from  the  living  tissues  into  the  current  of 
blood. 

It  has  not  yet  been  decided  whether  all  fat  passes  from  the 
intestine  into  the  lacteals,  or  whether  a  part  enters  the  blood 
directly  through  the  walls  of  the  capillaries  of  the  intestinal 
villi.  Even  if  a  portion  does  take  the  latter  path,  it  appears 
to  be  inconsiderable.  Zawilsky  found  very  little  fat  in  the 
blood  of  a  dog,  which  had  been  fed  on  a  highly  fatty  diet, 
and  whose  chyle  was  drawn  off.  If  fat  passed  into  the  cap- 
illaries of  the  intestinal  villi  to  any  extent,  we  should  expect 
to  find  that  an  abundant  diet  of  fat  would  be  followed  by  a 
perceptibly  larger  increase  in  the  portal  than  in  the  arterial 
blood.  Comparative  estimates,  made  in  Heidenhain' s  labora- 
tory, showed  that  there  was  the  same  amount  of  fat  in  both 


THE   PATHS   OF   ABSORPTION 


191 


kinds  of  blood.  ^     An  average  of  five  analyses  of  blood  from  the 
same  number  of  dogs  gave — 


Dry  residue. 


Amount  of  fat  in 
total  blood. 


Amount  of  fat  in 
dry  residue. 


Carotid  .    . 
Portal  vein 


22.34  per  cent. 

22.84 


0.86  per  cent. 
0.85 


3.65  per  cent. 
3.35 


The  only  question  that  remains  for  us  to  consider  refers 
to  the  path  the  Proteids  take  in  order  to  become  absorbed. 
There  are  special  difficulties  to  contend  against  in  experiments 
on  this  subject,  because  proteids  already  form  the  chief  con- 
stituents of  blood  and  lymph.  If  we  consider  how  large  is 
the  amount  of  blood  which  passes  through  the  intestinal  capil- 
laries, we  cannot  expect  to  be  able  to  trace  an  increase  of 
proteid  in  the  blood  in  consequence  of  intestinal  absorption. 
Ludwig  and  Schmidt-Mülheim  therefore  adopted  another 
method.  They  tied  the  thoracic  duct,  and  found  that  this  did 
not  in  any  way  prevent  the  absorption  of  the  proteid,  and  that 
therefore  the  proteid  takes,  the  other  path,  through  the  portal 
vein.     I  will  here  quote  one  of  these  experiments.^ 

Weight  of  dog,  14.73  kgrms.  The  dog,  which  had  pre- 
viously fasted  for  four  days,  passed  all  his  urine  before  the 
operation.  The  jugular  and  subclavian  veins  and  lymphatic 
ducts  on  both  sides  were  now  tied.  An  hour  after  the  opera- 
tion, and  again  on  the  following  afternoon,  the  dog  ate  on  each 
occasion  400  grms.  of  meat ;  and  the  whole  time  was  in  ex- 
cellent condition.  Forty-eight  hours  after  the  operation,  the 
animal  was  killed  by  opening  the  carotid.  On  post-mortem 
examination,  the  chyle  was  found  completely  shut  off  from  the 
blood-vessels.  The  alimentary  canal  contained  7.37  grms.  N. 
It  thus  appears  that  583.24  grms.  of  meat  were  absorbed  after 
complete  interruption  of  the  chyle-current.  The  urine  secreted 
after  the  operation  contained  21.95  N,  an  amount  correspond- 
ing to  the  food  absorbed. 

Four  other  experiments  carried  out  in  the  same  manner 
gave  the  same  result.  We  thus  see  that  proteid,  like  all  food- 
substances  dissolved  in  water,  enters  the  blood  directly  through 
the  walls  of  the  intestinal  capillaries. 

The  question  now  arises,  whether  all  proteid,  in  order  to  be 
able  to  follow  this  path,  must  be  peptonized  beforehand,  or 
whether  a  portion  of  the  proteid  is  absorbed  as  such. 

*  Heidenhain,  Pflüger's  Arch.,  vol.  xli.  Sup.,  p.  95  :  1888. 
2  Schmidt-Mülheim,  loc.  cit.,  p.  565,  Exp.  5. 


192  LECTUEE   XIII  ^ 

There  is  no  ä  priori  ground  for  supposing  that  proteid  is  not 
absorbed  unchanged.  If  fat-droplets,  visible  under  the  micro- 
scope, and  even  entire  leucocytes,  can  leave  the  blood-capillaries 
and  travel  through  the  tissues,  why  may  not  a  proteid  molecule 
find  its  way  through  the  capillary  wall?  Voit  and  Bauer 
have  endeavored  to  prove  this  experimentally/  A  coil  of 
small  intestine  of  a  live  dog  or  cat  was  cleansed  of  all  contents, 
and  a  piece  of  a  certain  length  was  tied  at  both  ends  with 
a  double  ligature ;  a  solution  of  proteid  was  then  injected  into 
this  ligatured  piece,  the  coil  replaced,  and  the  abdominal 
wound  closed.  The  percentage  of  proteid  contained  in  the 
solution  being  known,  the  operators  estimated  the  quantity 
injected  by  the  loss  of  weight  of  the  syringe  used.  After 
a  few  hours  the  animal  was  killed,  and  the  amount  of  proteid 
in  the  piece  of  intestine  was  estimated.  It  was  invariably 
found  that  a  considerable  portion  had  disappeared  in  from  one 
to  four  hours — from  16  to  33  per  cent,  of  egg-albumin,  from 
28  to  95  per  cent,  of  acid-albumin  prepared  from  muscle. 
Voit  and  Bauer  refute  the  obvious  objection  that  the  coil  of 
small  intestine  was  not  thoroughly  cleansed  from  the  peptic 
and  pancreatic  ferments,  as  they  found  that  the  remainder 
of  the  proteid  in  the  piece  that  had  been  tied  was  always  com- 
pletely coagulable  by  boiling.  No  peptone  was  present  with 
the  proteid. 

Voit  and  Bauer  have  also  injected  solutions  of  proteid  into 
the  rectum  of  fasting  dogs,  and  determined  the  absorption  of 
the  unchanged  proteid  from  the  increased  secretion  of  urea. 
Eichhorst  ^  draws  the  same  conclusion  from  similar  experiments. 
These  experiments  are  open  to  the  objection  that  the  pancreatic 
ferment  may  extend  into  the  rectum.  The  experiments  of 
Czerny  and  Latsch enberger,^  however,  are  free  from  this 
objection,  because  they  were  made  on  a  man  with  an  artificial 
anus  at  the  sigmoid  flexure.  The  rectum  could  be  syringed 
quite  clean  through  the  fistula.  If  a  solution  of  proteid  were 
then  injected,  and  the  rectum  again  washed  out  after  from 
twenty-three  to  twenty-nine  hours,  it  was  found  that  from  60 
to  70  per  cent,  of  the  proteid  had  disappeared.  Nencki  *  and 
his  pupils  came  to  the  same  conclusion  as  the  result  of  a 
similar  experiment  on  man. 

A  few  authors  have  gone  so  far  as  to  maintain  that  only 

1  C.  Voit  and  J.  Bauer,  Zeitschr.  f.  Biolog.,  vol.  v.  p.  562  :  1869. 
^Hermann  Eichhorst,  Pflüger's  Arch.,  vol.  iv.  p.  570 :  1871. 
^  V.  Czerny  and  J.  Latschenberger,  Virchow's  Arch.,  vol.  lix.  p.  161 :  1874. 
^  MacFadyen,  Nencki  and  Sieber,  JrcA.  /.  exper.  Path.  u.  Pharm., vol.  xxviii. 
p.  344 :  1891. 


THE    TATHS    OF    ABSORPTION  193 

the  unaltered  proteid  is  of  any  use  after  absorption  in  replacing 
the  proteid 'used  up  in  the  tissue,  and  that  the  peptones,  on  the 
contrary,  undergo  rapid  further  decomposition,  and  only  serve 
as  sources  of  energy. 

Certain  facts  seem  to  agree  with  this  view.  A  fasting 
animal  is  very  economical  with  its  store  of  proteid,  and  its 
excretion  of  urea  is  very  limited ;  whereas,  after  a  meal  con- 
sisting largely  of  proteids,  an  amount  of  nitrogen  closely  corre- 
sponding to  the  proteid  eaten  reappears  in  the  urine  in  the 
course  of  the  next  twelve  hours.  It  might  ä  priori  be  expected 
that  the  nitrogenous  equilibrium  would  be  maintained  if  a  fast- 
ing dog  were  to  eat  as  much  proteid  as  corresponds  to  the 
nitrogen  excreted  in  hunger,  together  with  plenty  of  non- 
nitrogenous  food.  It  might  be  thought  that  it  would  be  in- 
diiferent  whether  the  necessary  proteid  were  derived  from  the 
food,  or  from  the  animaPs  own  tissues.  But  it  is  not  so.  If 
a  fasting  dog  be  given  only  as  much  proteid  as  corresponds  to 
the  proteid  used  up  in  fasting,  it  still  goes  on  consuming  the 
nitrogenous  constituents  of  its  own  tissues.  Nitrogenous  equi- 
librium, i.  e.,  the  condition  in  which  the  animal  excretes  no 
more  nitrogen  than  he  takes  in,  is  not  established  until  three 
times  as  much  proteid  is  given. ^ 

Ludwig  and  Tschiriew  ^  injected  into  the  vein  of  a  dog 
defibrinated  blood  from  another  dog.  This  caused  only  an  in- 
considerable increase  of  nitrogenous  excretion.  But  if  they 
gave  the  dog  the  same  quantity  of  blood  by  the  mouth,  the  ex- 
cretion of  nitrogen  rose  proportionately  to  the  amount  given. 
Förster^  attained  the  same  result  in  similar  experiments. 
[Pflüger  however  has  shown  that  the  assimilation  of  serum  is 
as  complete  when  it  is  administered  intravenously  as  when  it  is 
given  by  the  mouth.] 

Proteid  therefore  behaves  very  differently  according  to  the 
way  in  which  it  reaches  the  blood  and  the  tissues.  When 
taken  up  from  the  intestine,  it  rapidly  undergoes  a  destructive 
metabolism. 

This  fact  was  quoted  in  support  of  the  theory  that  peptones 
are  not  assimilable.  It  was  claimed  that  proteids  absorbed 
from  the  intestine,  being  mostly  peptonized,  must  therefore  go 
on  decomposing  rapidly  ;  and,  further,  that  only  that  portion  of 
the  proteid  which  is  absorbed  as  such  can  be  used  in  building 
up  the  tissues. 

But  the  facts  are  capable  of  another  interpretation,  for  we 

^  Voit,  Zeitschr.f.  Biolog.,  vol.  iii.  pp.  29,  30  :  1867. 

^  S.  Tschiriew,  Arbeiten  au^  dem  physiol.  Institut  su  Leipzig,  p.  441  :  1874. 

^  J.  Forster,  Zeitschr.  f.  Biolog.,  vol.  ii.  p.  496  :  1875. 

13 


194  LECTURE   XIII 

now  know  that  the  peptones  are,  after  absorption,  regenerated 
into  proteid.  The  following  experiments  show  this  to  be  the 
case. 

Plosz  ^  fed  a  dog  ten  weeks  old  for  eighteen  days  on  an 
artificial  milk,  in  which  the  casein  and  the  proteids  were  re- 
placed by  peptones.  The  animal  kept  its  health  on  this  diet, 
and  its  weight  increased  from  1335  to  1836  grms.,  or  37.5  per 
cent.  It  is  very  improbable  that  the  weight  could  increase  so 
much  without  a  corresponding  growth  of  the  tissues  containing 
proteid,  which  must  therefore  have  been  formed  from  the  pep- 
tones of  the  food. 

Plosz  and  Gyergyai  ^  made  a  second  experiment  on  a  full- 
grown  dog.  The  animal  was  fed  for  six  days  on  an  artificial 
mixture,  containing  peptone  instead  of  proteid.  During  this  time 
the  weight  mcreased  somewhat,  and  the  excretion  of  nitrogen 
was  a  little  less  than  that  taken  in.  This  experiment,  again, 
can  only  be  interpreted  to  mean  that  proteid  had  been  formed 
from  the  peptones. 

The  proteid  stored  in  the  animal  tissues  may  come  from  two 
sources :  from  that  which  has  been  absorbed  unaltered,  and 
from  that  formed  by  the  regeneration  of  the  peptones.  But 
what  quantitative  proportion  do  they  bear  to  each  other? 
How  large  is  the  portion  of  the  proteid  of  the  food  which  is 
peptonized  in  the  intestine?  Schmidt-Mülheim^  tried  to  find 
an  answer  to  this  in  the  following  manner.  He  fed  six  dogs 
on  boiled  meat,  killed  them  one,  two,  four,  six,  nine,  and 
twelve  hours  after  the  meal,  and  examined  the  contents  of 
stomach  and  intestine.  In  each  case  he  found  considerably 
more  peptone  than  dissolved  proteid,  both  in  stomach  and  in- 
testine. It  thus  appears  that  the  greater  part  of  the  proteid 
became  absorbed  after  peptonization. 

What  is  the  fate  of  peptones  after  absorption  ?  They  are 
either  not  found  at  all  or  only  in  very  small  amount  in  the 
blood  of  digesting  animals.  Schmidt-Mülheim  gives  the  maxi- 
mum as  0.028  per  cent,  of  serum  ;  Hofmeister  found  that  it 
amounted  to  as  much  as  0.055  per  cent,  of  the  total  blood. 
Peptones  are  not  found  in  the  blood  of  fasting  animals.*  As 
might  be  expected,  they  cannot  be  detected  in  chyle,  not  even 

p.  Plosz,  Pfliiger's  Arch.,  vol.  ix.  p.  323  :  1874.  Compare  Maly,  ibid.,  vol. 
ix.  p.  609  :  1874. 

2  P.  Plosz  and  A.  Gyergyai,  ibid.,  vol.  x.  p.  545  :  1875. 

3  Schmidt-Mülheim,  Du  Bois'  Arch.,  p.  43  :  1879. 

"^  Ibid.,  pp.  38-42  :  1880;  Hofmeister,  Zeitschr.  f.  physiol.  CAem.,  vol.  v.  p. 
149  :  1881 ;  and  vol.  vi.  p.  60,  et  seq.  [The  small  amounts  of  peptone  found  by 
these  observers  are  due  to  errors  of  analysis.  The  blood  of  healthy  animals, 
whether  fasting  or  fed,  never  contains  the  slightest  traces  of  proteoses  or  peptones.] 


THE    PATHS    OF    ABSORPTION  195 

when  they  are  found  in  the  blood.^  If  peptone  be  injected 
into  the  blood,  it  passes  into  the  urine,^  and  none  can  be  traced 
in  the  blood  after  from  ten  to  sixteen  minutes.^  Hofmeister 
has  shown  also,  that  after  subcutaneous  injection  the  greater 
part  of  the  peptone — as  much  as  72  per  cent. — reappears  in 
the  urine.* 

As  normal  urine  never  contains  peptone,  the  peptone  ab- 
sorbed from  the  intestine  must  be  prevented  by  some  means  or 
other  from  passing  into  this  secretion.  The  larger  portion  does 
not  apparently  enter  the  general  circulation  as  peptone,  but  is 
previously  converted  into  proteid.  But  where  does  this  regen- 
eration of  peptone  to  proteid  take  place  ?  Is  it  in  the  liver  ? 
If  the  peptones  are  considered  as  decomposition-products  from 
proteid,  then  the  formation  of  proteid  from  peptone  would  be 
analogous  to  the  formation  of  glycogen  from  sugar  in  the  liver. 
But  the  portal  blood  either  contains  no  peptone,  or  not  more 
than  arterial  blood. ^ 

The  only  remaining  supposition  is  that  the  conversion  of 
peptones  into  proteid  takes  place  mostly  within  the  intestinal 
walls.  The  facts  observed  by  Hofmeister  are  in  harmony  with 
this  view.  He  most  carefully  examined  the  viscera  of  dogs 
while  digesting,  and  found  that  the  stomach  and  intestinal  wall 
are  the  only  parts  of  the  body  in  which  a  supply  of  peptone  is 
always  found  during  digestion.  In  most  cases  small  quantities 
of  peptones  were  also  found  in  the  blood,  and  in  four  out  of 
ten  cases  in  the  spleen.  No  peptone  was  ever  detected  in  any 
other  organs  or  tissues.^  Hofmeister  has  also  shown  that  the 
peptones  are  always  stored  in  the  mucous  membrane,  and  never 
in  the  muscular  walls  of  the  alimentary  canal.'' 

Lastly,  Hofmeister  has  discovered  the  important  fact  that 
peptone  soon  undergoes  a  change  in  the  gastric  and  intestinal 
wall.^  The  stomach  of  an  animal,  immediately  after  it  had 
been  killed,  was  divided  into  two  symmetrical  halves  by  in- 
cisions in  the  large  and  small  curvatures,  or  else  a  piece  of  in- 

1  Schmidt-Müllieim,  Du  Bois'  Arch.,  p.  41  :  1880  ;  Hofmeister,  Arch.  f.  exper. 
Path.  u.  Pharm.,  vol.  xix.  p.  17  :  1885. 

2  P.  Plosz  and  A.  Gyergyai,  Pflüger 's  ^rcA.,  vol.  x.  p.  552  :  1875;  Fr.  Hof- 
meister, Zeitschr.  f.  physiol.  Chem.,  vol.  v.  p.  131  :  1881. 

3  Schmidt-Mülheim,  Du  Bois' Arch.,  pp.  46-48  :  1880  ;  Fano,  ibid.,  p.  281 :  1881. 
[By  the  employment  of  trichloracetic  acid  as  a  precipitant  for  the  proteids,  it  is 
possible  to  detect  the  presence  of  peptone  in  blood  for  as  much  as  two  hours  after 
its  injection  into  a  vein.] 

4Fr.  Hofmeister,  Zeitschr.  f.  physiol.  Chem.,  vol.  v.  pp.  132-137  :  1881. 

5  Schmidt-Mülheim,  Du  Bois' Arch.,  p.  43  :  1880. 

6  Hofmeister,  Zeitschr.  f.  physiol.  Chem.,  vol.  vi.  p.  51  :  1882. 

'  Hofmeister,  Arch.  f.  exper.  Path.u.  Pharm.,  vol.  xix.  p.  9  :  1885. 
*  Hofmeister,  Zeitschr.  /.  physiol.  Chem.,  vol.  vi.  pp.  69-73;  and  Arch.f. 
exper.  Path.  u.  Pharm.,  vol.  xix.  pp.  8-15  :  1885. 


196  LECTURE   XIII 

testine  was  separated  by  two  incisions  lengthwise  into  two  equal 
portions.  The  mucous  membrane  was  washed  with  a  dilute 
solution  of  common  salt^  one  half  was  thrown  at  once  into  boil- 
ing water,  whereas  the  other  one  was  previously  put  for  a  little 
time  into  a  moist  chamber  at  40°  C.  Far  more  peptone  was 
always  found  in  the  first  half  than  in  the  second.  If  the 
second  half  were  not  placed  in  the  boiling  water  for  two  or 
three  hours,  no  peptone  was  ever  found  in  it.  It  is  for  teleo- 
logical  reasons  very  improbable  that  the  peptone  is  further 
split  up  in  the  mucous  membrane.  One  can  only  suppose  that 
the  peptone  is  reconverted  into  proteid  in  the  mucous  mem- 
brane of  the  digestive  canal.  That  it  is  a  vital  process  is 
rendered  probable  from  a  fact  observed  by  Hofmeister.  If  one 
half  of  the  stomach  were  thrown  at  once  into  boiling  water, 
and  the  other  kept  in  water  at  60°  C.  for  a  few  minutes  before 
being  placed  for  two  hours  in  a  temperature  of  40°  C,  the 
amount  of  peptone  proved  to  be  the  same  in  both  halves.  A 
temperature  of  60°  C.  has  been  found  by  experience  to  destroy 
living  animal  cells,  but  not  all  unorganized  ferments.  The 
conversion  of  peptone  into  proteid  must  therefore  be  brought 
about  by  the  vital  functions  of  the  surviving  cells  of  the  ex- 
tirpated stomach. 

The  following  observation,  made  by  Salvioli  ^  in  Lud  wig's 
laboratory  in  Leipzig,  perfectly  agrees  with  these  results  of 
Hofmeister's.  A  coil  of  small  intestine,  with  the  piece  ot 
mesentery  attached,  was  cut  out  of  a  dog  that  had  just  been 
killed.  One  gramme  of  peptone  in  10  c.cms.  solution  was 
placed  in  the  piece  of  intestine  and  the  ends  closed.  Then, 
after  tying  the  collateral  vessels,  a  current  of  warm  defibrinated 
blood,  diluted  with  a  solution  of  common  salt,  was  directed 
into  a  branch  of  the  mesenteric  artery  and  allowed  to  flow  out 
again  by  the  corresponding  vein.  Whilst  the  blood  circulated, 
the  intestine  showed  marked  peristalsis.  After  the  current 
had  lasted  four  hours,  the  intestinal  contents  were  examined 
and  were  found  to  consist  of  about  half  a  gramme  of  coagulable 
proteid,  with  mere  traces  of  peptone.  Nor  was  there  any 
peptone  in  the  blood  that  had  made  the  circuit.  But  if  peptone 
were  added  to  the  blood  beforehand,  it  was  always  found  un- 
altered at  the  end  of  the  experiment.  The  peptone  therefore 
disappears  in  the  intestinal  wall  on  the  way  from  the  intestinal 
contents  into  the  blood. 

I  must  now  return  to  an  observation  on  the  behavior  of 
peptones,  and  discuss  it  in  somewhat  greater  detail.  We  have 
seen  that  the  reconversion  of  peptones  into  proteid  within  the 

1  Gaetano  Salvioli,  Du  Bois'  Arch.,  Sup.,  p.  112 :  1880. 


THE    PATHS    OF    ABSOEPTION  197 

intestinal  wall  is  nsually  not  very  complete ;  a  part  of  the 
peptone  generally  passes,  unchanged  by  digestion,  into  the 
blood.  Now,  what  is  the  further  fate  and  the  significance  of 
this  portion  ?  Why  does  it  not  pass  into  the  urine,  considering 
that  the  peptone  artificially  introduced  into  the  blood  does  so 
at  once?  Hofmeister^  remarked  this  fact,  for  he  calculated 
that  the  amount  of  peptone  which  reached  the  blood  after 
subcutaneous  injection,  and  passed  into  the  urine,  was  much 
less  than  the  quantity  that  was  found  in  the  blood  of  animals 
while  digesting  and  which  did  not  pass  into  the  urine.  Thus 
the  peptone  that  has  entered  the  blood  from  the  intestine  be- 
haves diiferently  from  that  which  reaches  it  in  any  other  way. 
Hofmeister  explains  this  fact  by  saying  that  the  peptone  which 
has  reached  the  blood  from  the  intestine  is  not  contained  in  the 
plasma  but  in  the  lymph-cells.  The  reasons  which  cause  him 
to  adopt  this  view  are  as  follows : 

1.  Considerable  quantities  of  peptone  are  found  in  pus, 
and,  moreover,  principally  or  even  exclusively  in  the  pus-cells, 
which  are  identical  with  the  lymph-cells  and  the  colorless 
blood-corpuscles  or  leucocytes.^ 

2.  When  the  blood  of  an  animal  was  examined  during 
digestion,  the  serum  was  free  from  peptone  ;  whereas  the  upper- 
most layer  of  the  blood-clot,  which  always  exhibits  most  leuco- 
cytes (compare  Lecture  XIV.),  was  found  to  contain  0.09  per 
cent,  of  peptone.^ 

3.  The  percentage  of  peptone  in  the  spleen,  which  is  well 
known  to  contain  leucocytes  in  abundance,  was  always  found  to 
be  higher  than  that  in  the  blood  of  the  same  animal. 

4.  The  adenoid  tissue,  ^vhich  contains  a  moderate  number 
of  lymph-cells  in  famishing  and  hungry  dogs,  is  literally  over- 
flowing with  them  in  the  case  of  well-fed  dogs.'' 

5.  The  cells  in  the  adenoid  tissue  of  animals  while  digesting 
show  more  nuclei  undergoing  karyokinesis  than  those  of  fasting 
animals.^ 

Finally,  Hofmeister's  pupil,  J.  Pohl,^  has  shown  that  the 

^Hofmeister,  Zeitschr.  f. physiol.  Chem.,  vol.  v.  p.  148:  1881. 
^Ibid.,  vol.  iv.  p.  274,  et  seq.  :  1880. 

3  Ibid.,  vol.  vi.  p.  67  :  1882. 

4  Ibid.,  vol.  V.  p.  150  :  1881. 

5  Hofmeister,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xix.  p.  32  :  1885.  Com- 
pare also  vol.  XX.  pp.  291-305  :  1885  ;  and  vol.  xxii.  p.  306  :  1887.  [These  obser- 
vations of  Hofmeister's  possess  now  little  more  than  historic  interest,  as  the  pep- 
tone he  discovered  in  the  blood  was  certainly  produced  during  his  manipulations 
for  the  purposes  of  analysis.  The  peptone  found  in  the  spleen  has  been  shown 
lately  by  Hedin  to  be  due  to  the  presence  in  the  cells  of  this  organ  of  a  special 
proteolytic  ferment,  which  resembles  trypsin  in  the  products  of  its  action,  but 
requires  an  acid  medium.] 

6  Julius  Pohl,  ibid.,  vol.  xxv.  p.  31  :  1888. 


198  LECTUEE    XIII 

number  of  leucocytes  in  the  blood  increases  during  the  digestion 
of  food  rich  in  proteid,  but  not  during  the  absorption  of  carbo- 
hydrates, fats,  salts,  and  water.  Pohl  has  also  shown  that  this 
increase  of  leucocytes  proceeds  from  the  intestinal  wall,  for 
there  was  always  a  much  larger  number  in  the  intestinal  veins 
than  in  the  corresponding  arteries. 

Thus  it  appears  that  the  lymph-cells  serve  not  only  as  the 
means  of  transport  for  the  peptones  in  the  blood-current ;  their 
increase  and  growth  seem  to  be  intimately  connected  with  the 
absorption  and  assimilation  of  nitrogenous  food.  As  the  num- 
ber of  leucocytes  in  our  body  is  always  the  same,  it  follows 
that,  as  the  proteid  becomes  absorbed  and  new  cells  are  pro- 
duced by  division,  a  corresponding  amount  of  old  lymph-cells 
must  die  off  and  decay.  This  perhaps  partially  explains  the 
above-mentioned  fact,  that  the  absorption  of  large  quantities  of 
proteid  is  followed  by  rapid  destruction  of  a  corresponding 
amount  of  proteid. 

At  the  same  time,  we  are  not  bound  to  assume  that  all  the 
peptone  which  disappears  in  the  intestinal  wall  is  reconverted 
into  proteid  in  the  lymph-cells  of  the  adenoid  tissue,  and  that 
this  reconversion  takes  place  only  through  the  assimilation, 
growth,  and  division  of  lymph-cells.  Heidenhain  ^  has  called 
attention  to  the  fact  that  the  nuclei  undergoing  karyokinesis  in 
the  lymph-cells  of  adenoid  tissue  are  not  sufficiently  numerous 
to  justify  such  a  conclusion.  He  considers  that  the  recon- 
version of  the  peptones  into  proteid  may  occur  to  a  large 
extent  in  the  epithelial  cells,  which  then  surrender  it  to  the 
blood-plasma  of  the  capillaries  forming  a  network  around  the 
intestinal  villi,  immediately  below  the  epithelial  cells. 

We  must  now  consider  what  happens  to  the  peptone  which 
has  reached  the  blood  from  the  intestine.  As  already  men- 
tioned, it  very  soon  disappears  from  the  blood,  without  passing 
into  the  urine.  Where  does  it  undergo  a  change  ?  The 
conversion  does  not  take  place  in  the  blood  itself.  Hofmeister  ^ 
took  two  samples  of  blood  from  the  carotid  of  a  dog  during  the 
process  of  digestion.  The  first  was  immediately  tested  for 
peptone ;  the  second  was  kept  for  two  and  a  half  hours  at 
37°  C.  before  being  tested.  The  amount  of  peptone  was  found 
to  be  exactly  the  same  in  both  cases.  Hofmeister  also  laid 
bare  to  the  utmost  extent  the  carotid  and .  crural  arteries  of  a 
living  dog,  applying  ligatures  above  and  below  as  well  as  to  the 
lateral  branches.  After  half  an  hour  the  pieces  of  artery  which 
had  been   tied  were  taken  out  and  their   contents   removed. 

1  Heidenhain,  Pflüger's  Arch.,  Suppl.,  vol.  xli.  pp.  72-74  :  1888. 

2  Hofmeister,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xix.  p.  23  :  1885. 


THE    PATHS    OF    ABSOEPTIOX  199 

Peptone  was  found  in  them.  It  does  not  therefore  disappear 
in  the  blood,  and  must  consequently  pass  into  the  tissues  from 
the  capillaries/  [It  can,  in  fact,  be  detected  in  the  lymph 
flowing  from  the  thoracic  duct  withm  half  a  minute  of  its 
injection  into  the  blood-stream.] 

Armed  with  this  knowledge  concerning  the  behavior  of 
peptones  in  the  body,  we  are  now  in  a  position  to  explain  the 
hitherto  enigmatic  appearance  of  peptone  in  the  urine  in  cer- 
tain forms  of  disease.  We  have  seen  that  the  peptones  pass 
into  the  urine  as  soon  as  they  reach  the  blood  by  some  other 
means  than  from  the  intestine.  This  is  obviously  the  case  in 
all  those  pathological  processes  in  which  peptonuria  occurs. 
Probably  in  all  such  cases  there  is  a  pathological  disintegration 
of  necrotic  tissue,  as  the  result  of  which  peptone  is  formed  and 
is  absorbed  into  the  blood ;  ^  as  for  instance  in  those  diseases 
in  which  there  is  a  considerable  accumulation  and  decomposi- 
tion of  pus — in  empyema,  purulent  peritonitis,  pyelitis,  in  some 
cases  of  phthisis  with  large  cavities,  and  the  like.  The  appear- 
ance of  peptone  in  the  urine  in  the  stage  of  resolution  of 
croupous  pneumonia  may  be  explained  in  a  similar  manner  : 
the  peptone  reaches  the  blood  when  the  exudation  in  the  lung 
is  absorbed.  As  a  matter  of  fact,  Hofmeister  was  able  to 
demonstrate  the  presence  of  a  considerable  quantity  of  peptone 
in  the  infiltrated  pneumatic  lung. 

1  Hofmeister,  Arch.  f.  exper.  Path.  i,.  Pharm.,  vol.  xix.  p.  30  :  1885. 

2  E.  Maixner,  Prager  Viertelj.,  vol.  cxliii.  p.  75  :  1879  ;  Hofmeister,  Zeitschr. 
f.physiol.  Chem.,  vol.  iv.  p.  265  :  1880;  R.  von  Jaksch,  Zeitschr.  f.  klin.  Med., 
vol.  vi.  p.  413  :  1883 ;  H.  Pacanowski,  ihid.,  vol.  ix.  p.  429  :  1885. 


LECTURE  XIV 


THE    BLOOD 


Havixg  followed  the  course  of  the  food-stuifs  as  far  as  their 
entrance  into  the  bloody  we  will  now  proceed  to  consider  the 
blood  itself. 

The  first  thing  that  strikes  us  when  we  begin  to  examine 
the  blood,  and  that  which  oifers  the  greatest  difficulties  to 
chemical  analysis,  is  the  phenomenon  of  coagulation.  As  soon 
as  the  blood  leaves  the  vessels  of  the  living  animal,  a  part 
of  the  proteids  passes  from  the  apparently  soluble  into  the 
coagulated  condition.  The  quantity  of  this  colloid  substance, 
commonly  called  fibrin,  is  relatively  very  small.  It  does  not 
usually  exceed  from  0.1  to  0.4  per  cent,  of  the  weight  of 
the  blood.  Nevertheless  the  passage  of  this  small  amount 
into  the  coagulated  state  converts  the  whole  blood  into  a  more 
or  less  solid  jelly-like  mass.  On  standing,  this  mass  contracts, 
sometimes  to  half  of  its  original  volume,  and  squeezes  out  the 
contained  fluid,  whilst  the  corpuscles  are  almost  wholly  retained. 
Thus  the  coagulated  blood  separates  into  clot  and  serum. 
Serum  is  therefore  plasma  minus  fibrin  ;  the  clot  consists  of  the 
closely  packed  blood-corpuscles,  with  a  small  residue  of  serum 
and  the  coagulated  proteid,  or  fibrin. 

If,  however,  the  blood  be  beaten  with  a  glass  rod  whilst 
coagulation  is  proceeding,  the  coagulating  substance  attaches 
itself  to  the  rod  in  the  form  of  small  fibrous  masses, 
which  coalesce  with  one  another,  and  contract  round  the 
rod  so  that  they  can  be  removed  with  it.  In  this  way 
so-called  defibrinated  blood  is  obtained,  which  remains  fluid, 
and  consists  of  serum  with  blood-corpuscles  suspended  in 
it.  When  we  remember  how  great  a  tendency  to  pass  into 
a  coagulated  modification  is  shown  by  all  colloid  bodies, 
the  phenomenon  of  coagulation  ought  not  to  surprise  us. 
Moreover,  it  is  by  no  means  a  peculiarity  of  the  blood.  Lymph 
and  chyle  are  likewise  coagulable.  The  appearance  of  rigor 
mortis  in  dying  muscle  depends  upon  an  essentially  similar 
process,  and  it  is  probable  that  the  death  of  every  living 
vegetable   and    animal    tissue    is   accompanied    by   a    passage 

200 


THE    BLOOD  201 

of  a  part  of  the  proteid  constituents  from  the  fluid  to  the 
coagulated  state.  Coagulation  of  the  blood  is  therefore  not 
a  vital  process — it  indicates  the  commencing  dissolution  of  the 
dying  blood ;  hence  it  might  be  thought  that  the  subject  of 
coagulation  was  beyond  the  scope  of  physiology. 

The  coagulation  of  the  blood  however  subserves  a  very 
important  process  ;  it  greatly  aids  in  preventing  bleeding  when 
a  blood-vessel  is  injured,  and  so  far  it  may  be  considered  as 
a  physiological  process,  one  of  the  means  of  self-preservation 
possessed  by  the  organism. 

The  nature  and  causes  of  coagulation  possess  an  extreme 
interest  from  a  pathological  point  of  view.  For  it  is  well 
known  that,  under  certain  pathological  conditions,  coagulation 
of  the  blood  takes  place  in  the  vessels  during  life ;  and  this 
process  leads  to  disturbances  of  the  most  varied  character,  and 
may  be  a  cause  of  death. 

Hence  it  is  a  question  of  great  importance  to  know  what 
causes  the  blood  to  remain  fluid  under  normal  conditions  in  the 
vessels  during  life ;  what  the  exact  nature  of  the  whole  process 
is ;  what  the  substance  is  which  separates  out ;  and  what  the 
causes  of  its  separation  are.  In  spite  of  many  researches,  we 
are  not  yet  in  a  position  satisfactorily  to  answer  this  question. 
The  little  that  is  positively  known  we  will  consider  in  detail. 
First  of  all,  we  know  that  the  contact  of  the  blood  with  the 
normal  living  vessel- wall  prevents  coagulation.^  If,  in  a  living 
animal,  a  blood-vessel  be  tied  at  two  points,  the  enclosed  stag- 
nating blood  does  not  coagulate  for  several  hours,  but  it  does  so 
very  quickly  if  it  be  allowed  to  escape  from  the  vessel. 

Brücke  showed  that  the  blood  in  the  heart  of  the  tortoise 
remained  fluid  after  the  heart  had  been  removed  from  the  body, 
when  the  vessels  had  been  tied.  If  minute  glass  tubes  were 
inserted  into  some  of  the  vessels,  so  as  to  fit  them  exactly, 
and  to  prevent  the  blood  from  coming  into  contact  with  the 
wall  of  the  vessel,  it  was  found  that  the  blood  clotted  in  these 
tubes,  but  remained  fluid  elsewhere,  in  the  other  vessels  and 
in  the  heart.  Indeed,  Brücke  observed  that  any  foreign  body 
introduced  into  the  blood  became  covered  with  a  layer  of 
fibrin. 

When  a  vessel  is  ligatured,  the  blood  after  a  time  coagulates 
from  the  point  ligatured  down  to  the  first  branch  given  oif  from 
the  vessel.  The  coagulation  always  starts  from  the  ligatured 
spot,  where  the  endothelium  of  the  vessel  is  injured.  It  may 
also  be  supposed  that  the  whole  endothelial  lining,  from  the 

^  E.  Brücke,  Virchow's  ^rcÄ.,  vol.  xii.  pp.  81,  172  :  1857. 


202  LECTURE    XIV 

injured  spot  to  the  first  brauch,  is  altered  and  no  longer  normal, 
since  it  does  not  obtain  the  usual  amount  of  specific  nutriment 
in  consequence  of  the  stagnation  of  the  blood. 

In  this  way  the  occurrence  of  thrombosis,  in  consequence 
of  atheromatous  degeneration  of  the  lining  membrane,  or  as  the 
result  of  the  compression  of  the  vessel  by  a  new  growth,  &c., 
may  be  explained/ 

We  know  further  that  the  coagulation  of  the  blood  is 
constantly  preceded  by  the  death  and  breakmg  up  of  the 
white  blood-corpuscles.  It  would  appear  that  in  some  way 
or  other  the  products  of  the  breaking  down  of  leucocytes 
enter  into  the  formation  of  the  clot.^  Mantegazza  pointed 
out  that  only  those  fluids  are  spontaneously  coagulable  which 
contain  leucocytes,  such  as  blood,  lymph,  and  pathological 
transudations,^  and  that  the  fluids  lose  their  power  of  clotting 
as  soon  as  the  leucocytes  can  be  removed.  Johannes  Müller* 
had  shown  that,  if  frog's  blood  be  diluted  with  a  solution  of 
sugar  and  filtered,  the  large  red  blood-corpuscles  remain  in 
the  filter,  whereas  the  filtrate  coagulates.  Johannes  Muller 
therefore  concluded  that  the  coagulating  matters  arise  from 
the  plasma.  But  Mantegazza  showed  that  the  small  and 
soft  colorless  blood-corpuscles  get  through  the  filter  paper 
in  this  experiment,  and  that  if  the  colorless  corpuscles  are 
retained  by  the  use  of  very  fine  filter  paper,  the  filtrate  is  not 
coagulable.'^ 

When  Mantegazza  drew  a  silk  thread  through  the  vein  of  a 
living  animal,  he  found  that  in  two  minutes  it  was  covered  with 
leucocytes,  and  some  fibrin,  which  was  commencing  to  form 
round   them.     If    the   experiment   lasted   longer,    the   thread 

^  On  the  origin  of  thrombi  vide  Virchow's  researches  in  his  "  Gesammelten 
Abhandlungen  zur  wissenschaftlichen  Medicin,"  pp.  59-732  :  Frankfurt  a.  M., 
1856;  further  F.  W.  Zahn,  Virchow's  ^Irc/i.,  vol.  Ixii.  p.  81  :  1875;  and  J.  C. 
Eberth  and  C.  Schimmelbusch,  Virchow's  Arch.,  vol.  ciii.  p.  39  :  1886  ;  and  vol. 
cv.  pp.  331,  456  :  1886.  A  general  survey  of  the  literature  of  the  subject  is  given 
here. 

2  The  view  that  fibrin  arose  from  the  breaking  up  of  the  leucocytes  was  first 
adopted  by  William  Addison,  London  Medical  Gazette,  new  ser.,  vol.  i.,  for  the 
session  1840-1841,  pp.  477,  689;  and  by  Lionel  Beale,  Quar.  Journ.  of  Micros. 
Science,  v6\.  xiv.  p.  47:  1864;  subsequently  by  Paolo  Mantegazza,  "  Ricerche 
sperimentali  sull '  origine  della  fibrina  e  sulla  causa  della  coagulatione  del 
sangue":  Milano,  1871.  A  complete  account  of  this  work,  by  Boll,  appeared  in 
1871,  in  the  Centralhl.  f.  d.  med.  Wissensch.,  p.  709  ;  and  in  1876  Mantegazza 
published  his  work  in  German  in  Moleschott's  Untersuch,  z.  Naturlehre  des  Men- 
schen n.  der  Thiere,  vol.  xi.  pp.  523-577.  Compare  E.  Tiegel,  "Notizen  über 
Schlangenblut,"  Pflüger's  Arch.,  vol.  xxiii.  p.  278  :  1880. 

3  Mantegazza,  Moleschott's  Untersuch,  z.  Naturlehre,  vol.  xi.  pp.  552,  557. 

4  .Johannes  Müller,  Handb.  d.  Physiol,  des  Menschen,  4th  edit.,  vol.  i.  p.  104  : 
Coblentz,  1844. 

5  Mantegazza,  loc.  cit.,  p.  556. 


THE    BLOOD  203 

became  siirronnded  with  a  strong  white  coaguhim,  which  Avas 
always  crowded  with  leucocytes.  Other  foreign  bodies  intro- 
duced into  the  blood-current  behaved  hi  the  same  manner,  and 
moreover  the  rougher  their  surface  the  more  extensive  was 
the  coagulum,  and  the  more  readily  did  the  leucocytes  attach 
themselves  to  it.  Xo  coagulum  formed  round  a  smooth  thin 
platinum  wire.^ 

Zahn  ^  made  similar  experiments  with  the  same  result.  If 
he  introduced  small  glass  rods  with  smooth  surfaces  into  the 
heart  of  a  living  animal,  no  clot  was  produced.  But  if  he 
roughened  the  rod  with  a  file  before  insertion,  a  coagulum 
formed  on  the  uneven  surface.  Zahn  showed  further  that  a 
grouping  together  and  breaking  up  of  leucocytes  always  pre- 
cedes formation  of  a  thrombus. 

Finally,  Alexander  Schmidt  has  carried  out  very  extensive 
experiments  on  the  relation  of  colorless  blood-corpuscles  to 
coagulation.^  He  found  that  horse's  blood  was  very  suitable 
for  this  purpose,  being  possessed  of  two  peculiarities  in  which 
it  differs  from  the  blood  of  other  animals  hitherto  examined  : 
firstly,  it  clots  more  slowly  ;  and,  secondly,  the  red  blood-cor- 
puscles sink  far  more  rapidly.  It  is  thus  possible  to  remove 
the  plasma  which  remains  after  the  red  corpuscles  have  sunk 
to  the  bottom,  before  coagulation  sets  in.  By  the  use  of  cold, 
clotting  is  still  further  delayed.  If  the  blood  be  allowed  to 
run  from  a  horse's  vein  straight  into  a  vessel  surrounded  with 
ice,  the  red  corpuscles  fall  completely  to  the  bottom,  and  the 
specifically  lighter  colorless  cells,  which  sink  more  slowly, 
form  a  layer  over  the  red  corpuscles  (bufpy-coat).  The  larger 
portion  of  the  plasma  can  now  be  removed  and  filtered.  The 
colorless  cells  remain  in  the  filter,  owing  to  the  solid  con- 
sistency acquired  in  the  cold,  which  prevents  their  accommo- 
dation   to    the   form  of  the  filter-pores  and    their  consequent 

^  Mantegazza,  Moleschott's  Untersuch,  z.  Naturlehre,  vol.  xi.  pp.  558-563. 

2  F.  W.  Zalm,  loc.  cit.,  pp.  104-112. 

^  Alexandei'  Schmidt  has  published  an  account  of  the  main  facts  of  his  com- 
prehensive researches,  with  the  title,  "  Die  Lehre  von  den  fermentativen  Gerin- 
nungserscheinungen  iu  den  eiweissartigen  thierischen  Körperflüssigkeiten " 
(Dorpat,  C.  Mattiesen,  1S76).  Alexander  Schmidt's  more  recent  investigations 
on  the  coagulation  of  the  blood  are  contained  iu  the  dissertations  by  his  pupils 
for  their  doctorate  : — "  L.  Birk  and  J.  Sachsendahl,  1880;  X.  Bojanus  and  Ferd. 
Hoffmann,  1881 ;  Ed.  von  Samsou-Himmelstjerna  and  X.  Heyl,  1882  ;  H.  Feiertag, 
F.  Slevogt,  Fr.  Eauschenbach,  and  Ed.  von  Gotsehel,  1883 ;  0.  Groth  and  W. 
Grohmann,  1884;  and  Jacob  von  Samson-Hinimelstjerna,  1885.  Compare  O. 
Hammarsten,  Pfliiger's  Arch.,  vol.  xiv.  p.  211  :  1877;  and  vol.  xxx.  p.  4.37:  1883; 
L.  Fredericq,  Bullet,  de.  I' Acad.  roy.  de  Belg.,  ser.  ii.  t.  Ixiv.  Xo.  7:  Juillet, 
1877  ;  Ann.  de  la  Soc.  de  Med.  de  Gand.  :  1877 ;  "  ßecherches  sur  la  constitution 
du  plasma  sanguin,"  Gand,  Paris,  Leipzig,  1878;  and  L.  C.  Wooldridge,  "The 
Xature  of  Coagulation,"  1888. 


204  LECTURE    XIV 

passage ;  and  a  pure  clear  plasma  is  obtained  as  filtrate,  which 
now  clots  very  slowly  and  yields  a  very  slight  coagulum.  If 
leucocytes  from  the  filter  be  added  to  this  plasma,  abundant 
coagulation  takes  places.  If  all  the  blood,  the  coagulation  of 
which  had  been  prevented  by  cooling,  be  allowed  to  clot  at  the 
temperature  of  the  room,  the  firmest  coagulum  occurs  in  the 
buify-coat. 

My  Dorpat  colleague  has  repeatedly  been  so  kind  as  to 
show  me  these  experiments  with  the  uncoagulated  horse's 
blood.  The  amount  of  leucocytes  is  most  surprising.  They  are 
undoubtedly  far  more  numerous  than  in  defibrinated  blood. 
But  the  extraordinary  variety  of  the  forms  is  still  more 
astonishing :  from  the  smallest  colorless  corpuscles,  with  a 
diameter  hardly  greater  than  that  of  the  red  corpuscles,  such 
as  one  is  accustomed  to  see  in  defibrinated  blood,  to  the  large 
granulated  yellowish  cells  with  nuclei,  and  a  diameter  of  more 
than  double — (Schmidt's  granule  masses).^  After  complete 
coagulation,  these  granule  masses  disappear.  Schmidt  and  his 
pupils  say  that  they  have  watched  their  breaking  up  into 
minute  granules,^  and  the  gradual  change  of  the  latter  into 
the  fibrin-coagulum,  under  the  microscope.  These  granule 
masses,  and  the  transitional  forms  between  them  and  the 
ordinary  colorless  blood-corpuscles,  appear  to  be  much  less 
numerous  and  to  break  up  more  rapidly  in  the  blood  of  other 
mammals,  so  that  it  is  difficult  to  obtain  a  view  of  them  under 
the  microscope.^ 

We  are  unable  as  yet  to  decide  whether  the  debris  of 
leucocytes  are  themselves  a  part  of  the  material  which  forms 
the  coagulum,  or  whether  certain  products  of  decomposition, 
resembling  ferments,  give  the  impulse  for  the  passage  of 
certain  proteids  of  the  plasma  into  the  coagulated  modifica- 
tion. 

1  A  diagram  of  these  granule  masses  and  their  products  of  decomposition  is 
given  in  the  Dissertation  of  George  Semmer,  "  Ueber  de  Faserstoff  bildung  im 
Amphibien-  und  Vogelblute  und  die  Entstehung  der  rothen  Blutkörperchen  der 
Säugethiere  "  :  Dorpat,  Mattiesen,  1874. 

2  Mantegazza  also  noticed  the  granules  in  the  plasma  from  horse's  blood  {loc. 
CiL,  p.  563). 

3  With  the  aid  of  the  improved  microscopes,  small  granules  and  ' '  Plättchen  '^ 
have  recently  been  discovered  in  the  blood,  which  are  considered  to  be  form- 
elements,  and  are  supposed  to  participate  in  the  coagulation  of  the  blood. 
Alexander  Schmidt  explains  these  structures  as  being  the  debris  of  his  granule 
masses.  In  this  connection  vide  G.  Hayem,  Compt.  rend.,  vol.  Ixxxvi.  p.  58  : 
1878 ;  J.  Bizzozero,  Virchow's  Arch.,  vol.  xc.  p.  261:  1882  ;  M.  Löwit,  Sitzungsber. 
der  Wiener  Akad.,  vol.  Ixxxix.  p.  270;  and  vol.  xc.  p.  80  :  1884;  and  L.  C- 
Wooldridge,  in  the  "  Beiträge  zur  Physiologie,  Carl  Ludwig  zu  seinem  siebzig- 
sten Geburtstage  gewidmet  von  seinen  Schülern,"  p.  221  :  Leipzig,  Vogel, 
1887. 


THE    BLOOD  205 

The  following  observation  must  be  cited  as  being  particu- 
larly important.  It  appears  that  a  part  of  the  substances 
which  excite  coagulation  remains  in  the  blood  after  the 
separation  of  the  fibrin  Alexander  Schmidt  showed  that,  if 
defibrinated  blood  or  serum  be  added  to  lymph  or  to  serous 
transudations,  which  coagulate  very  slowly  of  themselves,  and 
give  very  little  fibrin,  the  fluid  would  soon  be  entirely  con- 
verted into  a  gelatinous  mass.  The  fluids  of  the  pleural  and 
the  pericardial  cavities  of  human  beings  and  of  horses  are 
usually  quite  free  from  lymph-cells,  and  therefore  uncoagu- 
lable.  But  they  coagulate  on  the  addition  of  blood-serum. 
The  fact  that  coagulation  occurs  in  the  vessels  after  the  trans- 
fusion of  defibrinated  blood  is  capable  of  the  same  explana- 
tion. Armin  Köhler^  showed  that  if  blood  were  taken  from 
a  rabbit,  defibrinated,  and  then  injected  into  the  vessels  of  the 
same  animal,  death  ensued  owing  to  clotting  in  the  vessels. 
For  this  reason,  the  therapeutic  use  of  transfusion  has  fallen 
into  disuse.^  An  important  contribution  to  the  explanation  of 
blood-clotting  has  been  afforded  by  Arthus  and  Pages,^  who 
have  shown  that  coagulation  is  prevented  if  all  the  lime  salts 
be  precipitated  from  the  plasma  by  the  addition  of  a  small 
quantity  of  sodium  oxalate  or  fluorid."* 

From  these  remarks  on  the  coagulation  of  the  blood  it 
may  be  seen  what  difficulties  have  to  be  encountered  in  the 
chemical  examination  of  the  blood,  and  especially  in  any 
attempt  to  obtain  a  separate  quantitative  analysis  of  plasma 
and  of  blood-corpuscles. 

The  pure  unaltered  plasma,  as  procured  from  horse's  blood, 
according  to  Alexander  Schmidt's  method,  has  never  been 
analyzed.  The  serum  has  been  analyzed,  and  the  composition 
of  the  plasma  has  been  deducted  from  that  of  the  serum.  It 
was  considered  that  the  composition  of  the  plasma  was  ascer- 
tained when  the  fibrin  was  added  to  the  serum.  But  we  now 
know  that  the  calculation  is  not  so  easy.  We  do  not  know 
which  constituents  of  the  plasma  take  part  in  the  coagulation, 
nor  which  products  of  the  decomposition  of  lymph-cells  pass 

1  Armin  Köhler,  "  üeber  Thrombose  und  Transfusion,  Eiter  und  septische 
Infection,  u.  deren  Beziehungen  zum  Fibrinferment  "  :  Dorpat,  1877. 

2  E.  von  Bergmann  has  published,  in  the  form  of  a  lecture,  a  very  interesting 
account  and  criticism  of  the  literature  on  the  transfusion  of  blood,  "  Die  Schick- 
sale der  Transfusion  im  letzten  Decennium"  :  Berlin,  Hirschwald,  1883.  Com- 
pare A.  Landerer,  Virchow's  Arch.,  vol.  cv.  p.  351 :  1886. 

^M.  Arthus,  "Recherches  zur  la  coagulation  du  sang,"  These,  Paris,  1890. 
Arthus  and  Pages,  Arch,  de  Physiol,  norm,  et  path.,  vol.  xxii.  p.  739  :  1890. 

^  [For  discussion  of  the  more  recent  work  and  views  on  the  subject  of  the 
coagulation  of  the  blood,  the  reader  is  advised  to  consult  the  article  on  this  sub- 
ject in  Shäfer's  "Text-book  on  Physiology,"  vol.  i.] 


206  LECTURE    XIV 

into  the  serum.  We  do  not  know  what  should  be  removed 
from  or  what  added  to  the  serum  in  order  to  determine  the 
composition  of  the  plasma. 

We  are  met  by  insuperable  difficulties  in  the  endeavor  to 
free  the  red  blood-corpuscles  from  the  serum,  and  to  analyze 
them  in  a  pure  state.  The  means  adopted  by  chemists  to 
separate  a  precipitate  from  a  solution  cannot  be  used  in  this 
case.  The  large  blood-corpuscles  of  amphibia  may  be  collected 
on  the  filter,  but  not  those  of  mammals.  This  is  not  due  to 
their  minuteness ;  for  they  are  far  larger  under  the  microscope 
than,  for  instance,  the  crystals  of  a  precipitate  of  sulphate  of 
barium  or  oxalate  of  lime,  which  do  not  go  through  the  filter. 
The  red  blood-corpuscles  pass  through  the  filter,  because, 
owing  to  their  soft  and  yielding  consistency,  they  adapt  them- 
selves to  the  form  of  the  filter-pores.  The  method  of  decanting 
remains  as  a  last  resource,  but  this  alone  does  not  suffice,  and 
must  be  followed  by  washing ;  but  what  liquid  will  serve  for 
this  purpose?  The  usual  medium,  water,  cannot  be  employed 
in  this  case,  for  as  soon  as  the  red  blood-corpuscles  come  into 
contact  with  water,  the  red  coloring  matter,  hemoglobin, 
is  dissolved.  Now,  as  this  forms  the  chief  constituent  of  the 
red  corpuscles,  nothing  remains  but  so-called  stromata,  re- 
duced, pale,  round,  very  feebly  refractive,  specifically  light 
cUbrisJ 

If,  instead  of  water,  a  dilute  salt  solution  of  a  certain 
concentration  be  employed,  i.  e.,  from  1^  to  3  per  cent,  of 
sodium  chlorid,  no  change  in  the  corpuscles  apparent  under 
the  microscope  takes  place.  If  the  solution  of  salt  is  stronger, 
they  shrink ;  if  more  dilute  they  swell,  and  lose  some  of  their 
hemoglobin  in  it. 

By  thus  decanting  and  washing  with  dilute  salt  solution, 
the  blood-corpuscles  of  defibrinated  blood  can  be  completely 
separated  from  all  the  constituents  of  serum.  But  do  they 
retain  their  original  constitution?  May  not  the  salt  or  the 
water  pass  into  the  blood-corpuscles ;  and,  on  the  other  hand, 
may  not  constituents  of  the  blood-corpuscles  have  passed  into 
the  salt  solution  by  osmosis  ?  We  can  only  be  certain  of  one 
thing,  and  that  is,  that  no  hemoglobin  has  escaped,  as  this 
would  be  at  once  discovered  by  its  brilliant  color.  It  is 
likewise  extremely  probable  that  the  genuine  colloid  sub- 
stances, the  proteids,  which  diffuse  with  great  difficulty,  do 
not  quit  the  blood-corpuscles.  We  are  therefore  in  a  position 
to  form  a  quantitative  estimate  of  the  quantity  of  hemoglobin 

1  For  the  properties  and  constitution  of  the  stromata,  vide  L.  C.  Wooldridge, 
Du  Bois'  Arch.,  p.  387  :  1881. 


THE    BLOOD  207 

and  of  proteid  in  the  corpuscles  of  a  definite  amount  of 
blood.  If  moreover  the  quantity  of  hemoglobin  and  of 
proteid  in  the  total  blood,  and  the  amount  of  proteid  in  the 
serum,  be  estimated,  we  are  in  possession  of  all  the  figures 
necessary  to  compute  the  proportion  that  the  weight  of  the 
serum  bears  to  that  of  the  blood-corpuscles  in  the  total  blood. 

This  is  the  method  of  quantitative  analysis  of  the  blood 
proposed  by  Hoppe-Seyler.^  An  example  will  serve  to  ex- 
plain the  method  of  computation.^ 

In  100  grms.  of  defibrinated  pig's  blood  were  found — 

\b\  1888  ~*"™^^'^=  18.90  Proteids +  liemoglobin. 

In  the  blood-corpuscles  of  100  grms.  of  the  same  blood  were 
found — 

(a)  15.04  1 

{b)  15.13    ^mean:  15.07  proteids  + hemoglobin. 

(c)   15.05  j 

In  the  serum  of  100  grms.  of  blood — 

18.90  —  15.07  =  3.83  grms.  proteids. 
In  100  grms.  of  serum — 

(h)   6'79    ^  average:  6.77  proteids. 

From  this  the  amount  of  serum  in  100  grms.  of  defibrinated 
blood  may  be  computed — 

- -^  •  100^56.6  per  cent,  serum. 

100  —  56.6  =  43.4  per  cent,  blood-corpuscles. 

Aji  analysis  of  the  total  blood  and  another  of  the  serum 
is  now  all  that  is  necessary  to  enable  us  to  compute  the  exact 
proportion  of  each  constituent  in  defibrinated  blood. 

In  order  to  prove  the  reliability  of  this  method,  I  deter- 
mined the  proportion  of  the  serum  to  the  corpuscles  in  the 
same  blood  by  another  method.  We  are  in  fact  able  to 
estimate  this  proportion,  as  soon  as  we  are  in  a  position  to 
ascertain  accurately  that  any  one  of  the  constituents  of  the 
serum   does   not   occur  in    the  corpuscles.     This   is  the   case 

^Hoppe-Seyler,  "  Handb.  der  physiol.  u.  pathol.  chemisch.  Analyse,"  §  272, 
5th  edit.,  p.  441  :  Berlin,  Hirschwald,  1883.  This  method  is  rendered  much  more 
simple  by  the  use  of  the  centrifuge  {vide  L.  von  Babo,  Liebig's  AnnaL,  vol. 
Ixxxii.  p.  301  :  1852);  without  this,  the  repeated  sinking  of  the  blood-corpuscles 
for  the  purpose  of  decanting  the  fluid  would  necessitate  a  process  occupying  sev- 
eral weeks,  and  even  at  a  low  temperature  decomposition  and  escape  of  hemo- 
globin would  be  unavoidable. 

2  G.  Bunge,  "  Zur  quantitativen  Analyse  des  Blutes,"  Zeitschr.  f.  Biolog., 
vol.  xii,  p.  191  :  1876. 


208  LECTURE   XIV 

with  sodium  in  some  kinds  of  blood.  It  was  rendered  prob- 
able by  the  earlier  experiments  of  C.  Schmidt  ^  and  of  Hoppe- 
Seyler's  pupil,  Sacharjin/  and  the  following  analyses  made 
by  myself  put  the  matter  beyond  all  doubt. 

If  defibrinated  pig's  blood  be  acted  on  by  the  centrifugal 
machine,  the  red  corpuscles  separate  from  the  serum  as  a 
thick  paste,  which  is  found  to  be  very  poor  in  sodium.  It 
contains  seven  times  less  sodium  than  the  serum.  Supposing 
the  deposit  to  contain  only  one-seventh  of  its  total  bulk  of 
serum,  this  would,  suffice  to  cover  its  whole  amomit  of  sodium. 
Now,  there  was  no  difficulty  iu  determining  by  the  microscope 
a  considerable  amount  of  interstitial  fluid  among  the  cor- 
puscles. If  the  blood-corpuscles  contain  any  sodium  at  all, 
it  must  be  present  in  exceedingly  mmute  quantities,  and  we 
should  commit  no  serious  error  in  determining  the  quantity  of 
serum  in  blood,  by  calculating  it  from  the  amount  of  sodium 
in  the  blood  and  the  serum. 

The  analysis  and  calculation  gave  the  following  results : — 
In  the  total  blood — 

\b)   0  2409  I'^ean:  0. 2406  per  cent.  Na^O. 
In  serum — 

[b]  0  4260  }°^e^°=  0.4272  per  cent.  NaA 

0.2406^^,„.       -,  „ 

w-TK^  X  1Ö0  =  56.3  per  cent,  serum. 

100  —  56.3  =  43.7  per  cent,  blood-corpuscles. 

The  numbers  agree  remarkably  with  those  obtained  for  the 
same  pig's  blood  by  Hoppe-Seyler's  method. 

In  the  case  of  the  blood  of  the  horse,  I  made  an  analysis 
according  to  Hoppe-Seyler's  method,  and  found  46.5  per  cent, 
serum,  and  53.5  per  cent,  corpuscles ;  by  means  of  the  sodium 
calculation,  the  result  was  46.9  per  cent,  of  serum,  and  53.1 
per  cent,  of  blood-corpuscles.  This  correspondence  cannot 
be  accidental.  We  must  conclude  from  it  (1)  that  Hoppe- 
Seyler's  method  gives  correct  results ;  and  (2)  that  in  the 
blood  of  the  pig  and  the  horse,  the  sodium  occurs  only  in  the 
plasma. 

Unfortunately  the  latter  conclusion  is  not  true  for  all 
varieties  of  blood.  In  dog's  and  bullock's  blood  the  corpuscles 
contain  sodium  as  well  as  the  serum.  The  easy  and  exact 
method  for  determinmg  the  relative  proportions  of  corpuscles 

^  C.  Schmidt,  "Charakteristik  der  epidemischen  Cholera":  Leipzig  and 
Mitau,  1850. 

2  G.  Sacharjin,  "  Zur  Blutanalyse,"  Virchow's  Arch.,  vol.  xxi.  p.  387  :  1861. 


THE    BLOOD 


209 


and  serum  .by  means  of  the  amount  of  sodium  is  in  so  far 
of  very  great  value,  as  it  enables  us  to  put  to  the  proof  other 
methods  which  are  applicable  to  all  varieties  of  blood. 

In  the  following  tables  the  results  of  my  analyses  of  blood 
are  given  : — 

One  Thousand  Grammes  of  Defibrinated  Blood  Contain — 


Pig. 

Horse. 

Bullock. 

436.8  Cor- 

563.2 

531.5  Cor- 

468.5 

818.7  COE- 

681.3 

puscles. 

Serum. 

puscles. 

Serum. 

PUSCLES. 

Serum. 

Water 

276.1 

517.9 

323.6 

420.1 

191.2 

622.2 

Solids 

160.7 

45.3 

207.9 

48.4 

127.5 

59.1 

Proteid  and  hemo- 

globin .    .    . 

151.6 

38.1 

— 

— 

123.6 

49.9 

Other  organic  sub- 

stances .    , 

5.2 

2.8 

— 

— 

2.4 

3.8 

Inorganic  substances 

3.9 

4.3 

— 

— 

1.5 

5.4 

K2O  . 

2.421 

0.154 

2.62 

0.13 

0.238 

0.173 

Na^O 

0 

2.406 

0 

2.08 

0.667 

2.964 

CaO  . 

0 
0.069 

0.072 
0.021 

— 

— 

0.005 

0.070 

MgO. 

0.031 

Fe^Os 

— 

0.006 

— 

— 

— 

0.007 

CI  .   . 

0.657 
0.903 

2.034 
0.106 

1.02 

1.76 

0.521 
0.224 

2.532 

PA- 

0.181 

Oae  thousand  grammes  Cor- 
puscles contain— 

One  thousand  grammes 
Serum  contain — 

Pig. 

Horse. 

Bullock. 

Pig. 

Horse. 

Bullock. 

Water 

Solids 

Proteid  and  hemo- 
globin 

Other  organic  sub- 
stances . 

Inorganic  substances 

K2O 

NasO 

CaO           

MgO 

Fe.,03 

CI                     ... 

PA 

632.1 
367.9 

347.1 

12.0 
8.9 
5.543 
0 
0 
0.158 

1.504 
2.067 

608.9 
391.1 

4.92 
0 

1.93 

599.9 
400.1 

387.8 

7.5 

4.8 

0.747 

2.093 

0 

0.017 

1.635 
0.703 

919.6 

80.4 

67.7 

5.0 

7.7 

0.273 

4.272 

0.136 

0.038 

3.611 

0.188 

896.6 
103.4 

0.27 
4.43 

3.75 

913.3 

86.7 

73.2 

5.6 

7.9 

0.254 

4.351 

0.126 

0.045 

0.011 

3.717 

0.266 

E.  Abderhalden  ^  has  carried  out  two    complete  analyses 


of  blood  according  to  this  method. 


^E.  Abderhalden   (Bunge's  laboratory),  ZeUschr.  f.  physiol.   Chem.,   vol. 
xxiii.  p.  521 :  1897. 

14 


210 


LECTUEE    XIV 


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212 


LECTCTEE   XIV 


In  order  to  give  an  idea  of  the  composition  of  human  blood, 
I  subjoin  the  analysis  of  my  revered  teacher,  Carl  Schmidt,^ 
one  that  has  not  yet  been  surpassed,  though  it  may  be 
remarked  that  the  method  employed  gave  too  high  an 
estimate  for  the  corpuscles  in  proportion  to  the  volume  of 
blood. 


BLOOD  OF  A  MAN  TWENTY-FIVE  YEARS  OF  AGE. 


One  Thousand  Grammes  of  Blood. 


513.02  BLOOD-COKPUSCLES. 

Water ;    •    •  349.69 

Substances  not  vaporizing  at 
120°      163.33 


Hematin  ... 

'Blood  casein,'  etc 
Inorganic  constituents 


7.70  (including  0.512  iron) 
151.89 
3.74  (excluding  iron) 


Chlorin    .    ._ 0.8981 

Sulphuric  acid 0.031 

Phosphoric  acid 0.695 

Potassium 1.586 

Sodium 0.241 

Phosphate  of  lime     ._  .    .    .  0.048 

Phosphate  of  magnesium    .  0.031 

Oxygen 0.206 


'Chlorid  of  potassium    . 

.    1.887 

Sulphate  of  potassium  . 

.    0.068 

Phosphate  of  potassium 

.    1.202 

Phosphate  of  sodium    . 

.    0.325 

Soda     .    .                .        . 

.    0.175 

Phosphate  of  lime     .    . 

0.048 

Phosphate  of  magnesium 

.    0.031 

Total 


3.736 


486.98  INTERSTITIAL  FLUID    (PLASMA). 

Water ;    •    •  439.02 

Substances  not  vaporizing  at 

120°  47.96 


Fibrin  3.93 

'Albumin,'  etc  _ 39.89 

Inorganic  constituents  ...      4. 14 

Chlorin    .    ._      1.7221 

Sulphuric  acid 0.063 

Phosphoric  acid  ..  0.071 

Potassium 0.153 

Sodium    .    .    ._ 1.661 

Phosphate  of  lime     ....  0.145 

Phosphate  of  magnesium     .  0.106 

Oxygen 0.221J 


'Sulphate  of  potassium      .  0. 137 

Chlorid  of  potassium    .    .    .  0.175 

Chlorid  of  .sodium     ....  2.701 

Phosi)hate  of  sodium    .    .    .  0.132 

Soda         0.746 

Phosphate  of  lime     ....  0.145 

Phosphate  of  magnesium     .  0.106 

Total 4.142 


Specific  Gravity  =  1.0599. 


1 C.   Schmidt,    "Charakteristik    der  epidemischen   Cholera,"   pp.   29,   .32; 
Leipzig  and  Mitau,  1850. 


THE    BLOOD 


213 


BLOOD  OF  A  MAN  TWENTY-FIVE  YEAES  OF  AGE— (ccmimucc?). 

1000  GRAMMES  OF  BLOOD-CORPUSCLES. 

Water :    ■    •  ^^^-^^ 

Substances  not  vaporizing  at 


120^ 


318.37 


Hematin 15.02  (including  0.998  iron) 

'Blood-casein,'  etc 296.07 

Inorganic  constituents  .    .    .      7.28  (excluding  iron) 


Chlorin        .....  1.750 

Sulphuric  acid        .....    0.061 

Phosphoric  acid 1.355 

Potassium 3.091 

Sodium 0.470 

Phosphate  of  lime  ._  .  .  .  0.094 
Phosphate  of  magnesium  .  0.060 
Oxygen    ...  .    .        0.401, 

Total  of  inorganic  constituents  (exclusive  of  iron 

Specific  Gravity  =  1. 0886. 


Sulphate  of  potassium  .    . 
Chlorid  of  potassium    .    . 
Phosphate  of  potassium 
Phosphate  of  sodium    .    . 

Soda 

Phosphate  of  lime     .    .    . 
Phosphate  of  magnesium 


0.132 
3.679 
2.343 
0.633 
0.341 
0.094 
0.060 

7.282 


1000   GRAMMES  OF  INTERSTITIAL  FLUID    (PLASMA). 

Water _    .    .  901.51 

Substances  not  vaporizing  at 
120°      ...  ....    98.49 

Fibrin  8.06 

'Albumin,'  etc._ 81.92 

Inorganic  constituents  ...      8.51 


Chlorin 3.536 

Sulphuric  acid 0.129 

Phosphoric  acid 0. 145 

Potassium  .    .        ..    0.314 

Sodium 3.410 

Phosphate  of  lime      _       .    .    0.298 

Phosphate  of  magnesium     .    0.218 

Oxygen 0.455 

Total  of  inorganic  constituents 
Specific  Gravity  =  1.0312. 

1000  GRAMMES  OP  SERUM. 

Water :    •    •  908.84 

Substances  not  vaporizing  at 


'Sulphate  of  potassium 

0.281 

Chlorid  of  potassium    .    . 

0.359 

Chlorid  of  sodium     .    .    . 

5.546 

Phosphate  of  sodium    .    . 

0.271 

Soda      .    .               .... 

1.532 

Phosphate  of  lime     .    .    . 

0.298 

Phosphate  of  magnesium 

0.218 

120° 


91.16 


Albumin,  etc 82.59 

Inorganic  constituents  ...      8.57 

Chlorin  _ 3.5651 

Sulphuric  acid    .    .        ...    0.130 

Phosphoric  acid 0.146 

Potassium 0.317 

Sodium 3.438 

Phosphate  of  lime     ....    0.300 

Phosphate  of  magnesium    •    0.220 

Oxygen 0.458 

Total  of  inorganic  constituents 
Specific  Gravity  =  1.0292. 


r  =  i 


Sulphate  of  potassium  .  . 
Chlorid  of  potassium  .  . 
Chlorid  of  sodium  .  .  . 
Phosphate  of  sodium 

Soda ,    . 

Phosphate  of  lime 
Phosphate  of  magnesium 


8.505 


0.283 
0.362 
5.591 
0.273 
1.545 
0.300 
0.220 

8.574 


214 


LECTUEE    XIV 


BLOOD  OF  A  WOMAN   THIKTY  YEAES  OF  AGE. 
One  Thousand  Grammes  of  Blood. 

396.24  BLOOD-COKPUSCLES. 

Water  ...               ._          .  272.56 
Substances  not  vaporizing  at 
120°      123.68 


Hematin  . 

'  Blood-casein,'  etc.    . 

Inorganic  constituents 


6.99  (including  0.489  iron) 
113.14 
3.55  (excluding  iron) 


1.412 
0.648 

0.086 

0.370 


Chlorin 0.6431 

Sulphuric  acid    .    .    .  0.029 

Phosphoric  acid 0.362 

Potassium    . 

Sodium    .    .  ... 

Phosphate  of  lime    .    .    . 

Phosphate  of  magnesium 

Oxygen 


>  =  i 


'Sulphate  of  potassium  . 
Chlorid  of  potassium 
Phosphate  of  potassium 
Potash      ...... 

Soda     ...  ... 

Phosphate  of  lime    .    .    . 
Phosphate  of  magnesium 


Total  of  inorganic  constituents  (excluding  iron) 


603.76  INTERSTITIAL  FLUID  (PLASMA). 

Water  ...  .    .  551.99 

Substances  not  vaporizing  at 

120°  51.77 

Fibrin  1.91 

Albumin,  etc 44.79 

Inorganic  constituents  5.07 

Chlorin    .    ._ 2.2021 

Sulphuric  acid 0.060 

Phosphoric  acid  0. 144 

Potassium    ...  ..  0.200 

Sodium 1.916 

Phosphate  of  lime    .    .    . 
Phosphate  of  magnesium 

Oxygen 0.211, 


0.332 


y  =  < 


Sulphate  of  potassium 
Chlorid  of  potassium 
Chlorid  of  sodium     . 
Phosphate  of  sodium 
Soda  .  ■    ■    • 

Phosphate  of  lime    .    .    . 
Phosphate  of  magnesium 


0.062 
1.353 
0.835 
0.340 
0.874 

0.086 


3.550 


0.131 

0.270 
3.417 
0.267 
0.648 

0.332 


Total  of  inorganic  constituents 5.065 

Specific  Gravity  =  1 .  0503. 


1000  GRAMMES  OF  BLOOD-CELLS. 

Water       687.88 

Substances  not  vaporizing  at 

120°      312.12 

Hematin      18.48  (including  1.229  iron) 

'Blood-casein,'  etc.   .    .    .'  .  284.68 

Inorganic  constituents  ...      8.96  (excluding  iron) 


Chlorin 1.6231 

Sulphuric  acid 0.072 

Phosphoric  acid 0.913 

Potassium    .    .  ....    3.565 

Sodium        .     _ 1.6.35 

Phosphate  of  lime    .    .    .   \    q  ^j^g 
Phosphate  of  magnesium   / 
Oxygen 0.933J 

Total  of  inorganic  constituents  (excluding"! 
iron  of  hemoglobin)  J 

Specific  Gravity  =  1.0883. 


'Sulphate  of  potassium  . 
Chlorid  of  potassium  . 
Phosphate  of  potassium 

Potash  

Soda     ....... 

Phosphate  of  lime     .    .    .  \ 
Phosphate  of  magnesium    J 


0.157 
3.414 
2.108 
0.857 
2.205 

0.218 


8.959 


THE    BLOOD 


215 


BLOOD  OF  A  WOMAN  THIETY  YEAKS  OF  A.GY^{continued). 

1000  GRAMMES  OF   INTERSTITIAL  FLUID. 

Water  914.25 

Substances  not  vaporizing  at 

120°      ....  ...    85.75 


Fibrin 3.16 

Albumin,  etc.                 .    .    .  74.20 

Inorganic  constituents  ...  8.39 

Chlorin 3.6471 

Sulpburic  acid 0.100 

Phosphoric  acid     ....  0.237 

Potassium 0.332 

Sodium 3.173 

Phosphate  of  lime    .    .    . 
Phosphate  of  magnesium 

Oxygen    .       ......  0.351 


0.550 


Sulphate  of  potassium  0.217 

Chlorid  of  potassium    .    .    .  0.447 

Chlorid  of  sodium     ....  5.659 

Phosphate  of  sodium    .    .    .  0.443 

Soda      ........  1.074 

Phosphate  of  lime    .    .       1  n  ^«^0 
Phosphate  of  magnesium    J 


Total  of  inorganic  constituents 8.390 

Specific  Gravity  =  1.0269. 


1000  GRAMMES  OF  SERUM. 

Water _    .    .  917.15 

Substances  not  vaporizing  at 


120° 


82.85 


Albumin,  etc 74.43 

Inorganic  constituents  .    .  8.42 

Chlorin            3.6591 

Sulphuric  acid 0.100 

Phosphoric  acid         ....  0.238 

Potassium 0.333 

Sodium                3.183 

Phosphate  of  lime 

Phosphate  of  magnesium 

Oxygen 0.351 


0.552 


'Sulphate  of  potassium  .    .    .  0.218 

Chlorid  of  potassium  0.448 

Chlorid  of  sodium     ....  5.677 

Phosphate  of  sodium    .    .    .  0.444 

Soda 1.077 

Phosphate  of  lime               \  ^  p.^„ 

Phosphate  of  magnesium    J  ^-om 


Total  of  inorganic  constituents 8.416 

Specific  Gravity  ^1.0261. 


Hemoglobin  ^  therefore  is  the  only  organic  substance  which 
is  peculiar  to  the  red  corpuscles.  It  also  forms  the  chief  con- 
stituent of  the  dried  corpuscles.  We  have  already  considered 
the  composition  of  hemoglobin  and  the  question  of  its  origin, 
and  we  shall  shortly  have  to  discuss  the  importance  of  hemo- 
globin in  respiration  (Lecture  XVII.).     The  products  of  de- 

1  A  description  of  all  the  physical  and  chemical  properties  of  hemoglobin 
would  be  beyond  the  scope  of  the  present  text-book.  I  therefore  refer  the  reader 
to  the  accounts  of  Hoppe-Seyler  in  his  3Ied.  chem.  Unters. :  Berlin,  1866-1871  • 
and  to  those  of  Hiifner  and  his  pupils  in  the  Zeitschr.  f.  physiol.  Chem. ;  and  in 
the  latest  volumes  of  the  Journ.  f.  prakt.  Chem.  Compare  also  Nencki  and 
Sieber,  Arch.f.  exper.  Path.  u.  Pharm.,  vol.  xviii.  p.  401 :  1884 ;  and  vol  xx  pp 
325,332:  1886. 


216  LECTURE    XIV 

composition  will  also  be  considered  at  a  later  period  (Lectures 
XXI.  and  XXII.). 

The  organic  substances  found  in  serum  are  proteid,  fat, 
soaps,  Cholesterin,  lecithin,  sugar,  urea,  kreatin,  and  a  yellow 
coloring  matter  soluble  in  alcohol  and  ether,  called  lutein. 
Among  the  proteids,  which  make  up  the  chief  part  of  the 
organic  substances,  two  groups  are  to  be  distinguished,  the 
albumins  and  the  globulins.  The  former  are  soluble,  the 
latter  insoluble,  in  water,  but  globulins  are  dissolved  by  dilute 
solutions  of  sodium  chlorid.  If  serum  be  subjected  to  dialysis, 
the  salts  of  the  alkalies  diffuse  and  the  globulins  are  pre- 
cipitated, whilst  the  albumins  remain  dissolved.  The  relative 
proportion  of  the  two  varies  much.  The  result  of  starvation 
is  to  reduce  the  quantity  of  albumin  and  to  increase  the 
quantity  of  globulin.  It  would  thus  appear  that  globulin 
is  the  form  which  proteid  assumes  in  its  transference  from 
one  organ  to  another.  We  know  that  in  starvation  the  more 
important  organs,  the  centers  of  life,  are  nourished  at  the  ex- 
pense of  the  other  organs,  chiefly  of  the  skeletal  muscles.^  Thus 
Voit  ^  found  that  the  brain  and  spinal  cord  of  a  cat,  after  thir- 
teen days'  starvation,  had  lost  only  3.2  per  cent,  of  its  weight, 
the  heart  only  2.6  j)er  cent.  ;  the  skeletal  muscles,  on  the  other 
hand,  30.5  per  cent.  Miescher  found,  in  his  observations  al- 
ready quoted  (p.  79),  that  the  Rhine  salmon,  during  its  so- 
journ in  fresh  water,  eats  nothing,  and  that  the  organs  of  re- 
production, ovary  and  testes,  increase  at  the  expense  of  the 
muscles.  Miescher^  at  the  same  time  called  attention  to  the 
fact  that  during  this  period  the  globulins  of  the  blood,  which 
are  so  similar  to  those  of  muscle,  increase  in  quantity,  and  the 
maximum  of  this  increase  was  found  to  correspond  to  the  period 
of  maximum  growth  of  the  ovary. 

E.  Tiegel*  found  in  the  blood  serum  of  snakes,  whose 
alimentary  canal  was  empty,  only  globulin,  and  no  albumin  ; 
whereas  in  the  blood  of  snakes  whilst  digesting,  both  varieties 
of  proteid  were  constantly  present.     Burckhardt,^  Miescher's 

1  Chossat,  Mem.  presentes  ä  I' Acad,  des  Sciences  de  I' Institut  de  France  :  vol. 
viii. :  1843  ;  Bidder  and  Schmidt,  "  Die  Verdauungssäfte  u.  der  Stoffwechsel,"  p. 
327 :  1852. 

2  C.  Voit,  Zeitschr.  f.  Biolog.,  vol.  ii.  p.  355  :  1866. 

^  F.  Miescher-Riisch,  "  Statistische  u.  biologische  Beiträge  zur  Keniitniss 
vom  Leben  des  Rheinlachses."  Separatabdruck  aus  d.  Schweiz.  Literatursamm- 
lung zur  internationalen  Fischereiausstellung  in  Berlin,  1880,  p.  211. 

*  E.  Tiegel,  Pflüger's  Arch.,  vol.  xxiii.  p.  278  :  1880. 

5  Burckhardt,  Arch.  f.  exper.  Path.,  vol.  xvi.  p.  322:  1883.  The  apparently- 
contradictory  results  of  G.  Salvioli  are  probably  due  to  the  fact  that  the  period  of 
starvation  was  very  short  in  his  experiments.  Moreover  Salvioli  used  another 
method  for  separating  the  two  proteids  (Du  Bois'  Arch.,  p.  268 :  1881). 


THE    BLOOD  217 

pupil,  has  shown  that  the  globulins  in  the  blood  of  starving^ 
animals  are  increased  at  the  expense  of  the  albumins. 

The  conclusions  of  Danilewsky/  that  the  muscles  of  an 
animal  which  have  the  least  work  to  do  are  richest  in  globulin, 
harmonize  with  these  observations.  It  would  appear  that  the 
muscles  are  not  only  organs  of  locomotion,  but  also  storehouses 
for  proteid. 

'  A.  Danilewsky,  Zeitschr.  f.  physiol.  Chem.,  vol.  vii.  p.  124:  1882. 


LECTURE  XV 


LYMPH.^ 

The  substances  which  pass  from  the  blood  into  the  other 
tissues,  there  to  be  used  up  by  the  cells  as  food,  do  not  reach 
these  elements  directly  through  the  capillary  wall ;  but  proceed 
first  into  the  lymph  spaces,  which  are  present  in  all  the  tissues. 
In  the  same  manner,  the  final  products  of  the  metabolism  of 
each  cell  do  not  pass  straight  into  the  blood,  but  must  first  be 
taken  up  by  the  lymph  which  bathes  all  the  tissue-elements. 

The  only  exception  to  this  rule  is  furnished  by  Bowman's 
capsule  in  the  kidney,  which  is  closely  applied  to  the  walls  of 
the  blood-vessels  of  the  glomerulus  without  the  intervention  of 
any  appreciable  lymph  space.  This  arrangement  seems  to  be 
connected  with  particularly  rapid  and  complete  transference  of 
urinary  constituents  from  the  blood  to  the  renal  tubules.  If 
we  consider  how  large  an  amount  of  urea  is  excreted  by  these 
paths,  or  moreover  that  only  a  small  proportion  of  the  total 
arterial  blood-stream  passes  through  the  kidneys  and  remains 
but  a  short  time  in  these  organs,  we  shall  see  how  necessary 
some  such  arrangement  is. 

Such  a  rapid  passage  of  material  from  the  blood  does  not 
appear  to  be  essential  in  the  other  organs.  Most  physiologists 
have  therefore  conceived  the  idea  that  a  large  quantity  of  plasma 
is  always  proceeding  through  the  capillary  walls  into  the  lymph 
spaces,  thence  penetrating  the  tissues,  where  every  cell  extracts 
the  substance  which  it  needs  for  its  sustenance. 

■^  [Throughout  this  chapter  the  author  takes  no  notice  of  any  work  on  the 
subject  of  lymph-formation  since  the  publication  of  Heidenhain's  paper  in  1891. 
For  an  account  of  the  present  state  of  the  question  the  reader  is  referred  to 
Schäfer's  "Text-book  of  Physiology,"  vol.  i.  p.  285,  et  seq.  It  may  here  be 
merely  mentioned  that  recent  experiments  of  Starling,  Cohnstein  and  others 
have  tended  to  show  that  mechanical  factors  play  a  much  larger  part  in  the  pro- 
duction and  absorption  of  lymph  than  was  imagined  by  Heidenhain.  Ludwig 
ascribed  the  formation  of  lymph  to  the  cooperation  of  several  factors  :  (1)  Filtra- 
tion, depending  on  the  difference  of  pressure  between  the  blood  in  the  capillaries 
and  the  extravascular  fluid,  and  on  the  permeability  of  the  capillary  wall ;  and 
(2)  on  the  osmotic  interchanges  determined  by  chemical  changes,  i.  e.,  metabolic 
activity  of  the  tissue-cells.  Recent  investigations  have  served  to  confirm  rather 
than  to  refute  Ludwig's  ideas  on  the  subject.] 

218 


LYMPH  219 

This  interpretation  seemed  to  be  justified  by  the  circum- 
stance that  the  qualitative  composition  of  the  lymph  is  identical 
with  that  of  the  plasma.  Quantitatively  however  there  is  a 
difference ;  for,  while  the  inorganic  salts  contained  in  the 
lymph  are  alike  in  amount  and  composition  to  those  in  the 
plasma,  the  amount  of  proteid  in  the  lymph  is  much  smaller 
than  in  the  blood-plasma. 

No  definite  conception  has  been  formed  concerning  the 
mode  in  which  the  constituents  of  the  plasma  traverse  the 
capillary  wall.  It  is  not  possible  that  they  can  pass  through  by 
diffusion,  since  the  colloid  proteid  would  be  left  behind  in  the 
blood.  The  filtration  hypothesis  is  equally  untenable,  since  by 
this  means  all  the  constituents  of  the  plasma  would  proceed  to 
the  lymph  spaces  in  the  same  proportion  as  they  occur  in  the 
blood.  A  compromise  was  therefore  struck  between  diffusion 
and  filtration,  and  it  was  sought  to  explain  that  the  lymph  is 
rich  in  diffusible  constituents — salts,  and  relatively  poor  in  non- 
diffusible  substances — proteids.  Only  a  very  hazy  notion  could 
be  formed  concerning  the  nature  of  this  process,  therefore  a 
suitable  epithet  was  hailed  in  the  word  "  transudation,"  the 
lymph  being  called  the  "  transudate  of  the  plasma." 

These  theories  had  to  be  abandoned  when  the  processes 
came  to  be  tested  quantitatively  by  measuring  the  lymph- 
stream. 

In  twenty-four  hours  about  600  c.cm.  of  lymph  flows  through 
the  thoracic  duct  of  a  dog  10  kg.  in  weight.^ 

If  we  assume  that  the  flow  of  lymph  is  as  slow  in  man  as  in 
the  dog,  it  would  amount  to  about  4  liters,  in  proportion  to  the 
body-weight.  The  small  quantity  of  lymph  flowing  through 
the  right  thoracic  duct  into  the  blood  may  be  disregarded. 

This  stream  of  lymph  is  much  too  slow  to  justify  the 
assumption  that  all  the  cells  derive  their  nourishment  from  it. 
This  statement  may  be  proved  by  a  simple  calculation. 

Normal  plasma  contains  only  from  1  to  2  grm.  sugar  to 
the  liter.  In  the  course  of  the  twenty-four  hours  therefore  at 
most  8  grms.  of  sugar  would  be  conveyed  to  the  tissues  in  the 
4  liters  of  transuded  plasma.  This  amount  is  certainly  not  a 
sufficient  one.  As  a  matter  of  act  in  one  day  500  to  1000  grms. 
of  sugar  are  taken  up  from  the  intestines  into  the  blood  (Lecture 
XIIL).  This  amount  is  not  destroyed  in  the  blood  itself  (compare 
Lecture  XVII.).  It  must  therefore  reach  the  tissues  through 
the  capillary  walls.  Hence  it  follows  that  a  very  concentrated 
solution  of  sugar  traverses  the  cell-walls  in  those  tissues  where 

1  Vide  Heidenhain,  Pfliiger's  Arch.,  vol.  xlix.  p.  216 :  1891.  There  the  figures 
for  the  amounts  of  lymph  in  dogs  are  given.     Compare  also  Lecture  XIII. 


220  LECTURE   XV 

a  rapid  consumption  of  sugar  as  a  source  of  energy  takes  place, 
as  for  instance  in  the  muscles,  or  where  there  is  a  storing  up 
of  material  free  from  nitrogen,  such  as  glycogen  or  fat,  as  in. 
the  liver  or  in  the  connective  tissues/ 

We  may  adduce  another  example.^  The  milk  of  animals, 
which  develop  rapidly  is  very  rich  in  lime.  Dog's  milk  has 
from  4  to  5  grms.  of  lime  to  the  liter.^  A  bitch  from  20  to  30 
kg.  bodyweight  secretes  in  twenty-four  hours  as  much  as  ^ 
liter  of  milk,  which  contains  therefore  from  2  to  2|^  grms.  of" 
lime.  A  liter  of  plasma  contains  only  about  0.2  grm.  of  lime,* 
or  from  10  to  12  times  less  than  the  milk.  If  therefore  the 
epithelial  cells  of  the  mammary  glands  take  the  material  they 
need  for  the  formation  of  the  milk  from  the  transuded  plasma,, 
at  least  10  liters  of  plaSma  would  have  to  flow  through  the 
mammary  glands  in  the  twenty-four  hours.  This  is  not  possible  : 
only  from  1  to  2  liters  of  lymph  flow  through  the  whole  body — 
how  much  less  therefore  must  flow  through  the  mammary  glands  ? 
Hence  it  follows  that  a  fluid  very  rich  in  lime  must  be  exuded 
from  the  blood  capillaries  in  their  course  through  the  mammary 
glands,  or,  in  other  words,  that  the  endothelial  cells  of  the 
capillary  wall  must  exercise  a  power  of  selection,  as  in  fact  does 
every  cell,  every  living  being. 

That  the  capillary  wall  is  able  to  give  out  substances  in  a, 
much  more  concentrated  state  of  solution  than  that  in  which 
they  are  contained  in  the  plasma  may  be  seen  from  the 
capillaries  of  the  kidney.  The  plasma  contains  at  most  1  grm. 
urea  to  the  liter,  the  urine  may  contain  as  much  as  40  grm.  or 
even  more.^  Heidenhain  ^  has  shown  that,  after  the  injection 
of  solutions  of  sugar  into  the  blood,  the  amount  of  sugar  in 
the  lymph  rises  more  than  that  in  the  blood  plasma. 

1  [This  and  the  following  example  will  serve  as  a  criticism  of  the  views  of" 
Bartholini  but  not  of  those  of  Ludwig.  The  passage  of  sugar  or  other  diffusible 
substance  from  blood  to  tissue-cell  occurs  by  diffusion.  The  consumption  of  any 
substance,  whether  it  be  oxygen  or  glucose,  by  a  tissue-cell,  leads  to  a  diminished 
tension  of  this  substance  in  the  neighborhood  of  the  cell ;  and  a  passage  by 
diffusion  of  the  substance  naturally  occurs  from  blood  through  lymph-space  to 
cell.  Such  a  process  is  absolutely  independent  of  lymph-flow,  and  would  occur  if 
there  were  no  fresh  lymph  production  at  all.  An  argument  therefore  as  to  the 
concentration  of  the  transudation  from  the  vessels  which  is  based  on  the  con- 
sumption of  a  substance  by  any  given  tissue,  has  no  bearing  on  the  point  in 
question.] 

2  These  two  examples  were  introduced  by  myself  as  arguments  against  the- 
prevailing  views  on  the  flow  of  plasma  at  the  International  Physiological  Congress, 
held  at  Basel  in  September,  1889,  during  the  discussion  which  arose  after- 
Heidenhain's  address. 

3  Bunge,  Zeitschr.  f.  Biolog.,  vol.  x.  pp.  301  and  303  :  1874. 

*  In  1  liter  of  dog's  serum  I  found  0.176  CaO.    The  figure  must  be  some- 
what raised  for  the  plasma,  since  a  little  lime  is  carried  down  with  the  fibrin. 
5  Vide  Lecture  XXI.  for  the  composition  of  urine  in  man  when  on  a  meat  diet». 
•^  Log.  cit.,  p.  63,  et  seq. 


LYMPH  221 

In  every  organ  and  in  every  tissue  the  capillary  wall  allows 
a  fluid  of  special  constitution  to  pass  through  it,  according  to 
its  various  requirements  :  in  the  muscles  this  fluid  is  richer  in 
ßugar,  in  the  mammary  glands,  in  lime,  and  so  on.  After  these 
special  substances  have  been  utilized,  these  fluids  flow  back 
into  the  main  lymph-trunks,  so  that  the  mixture  takes  on  a 
•composition  very  similar  to  that  of  the  original  plasma.  The 
lymph  is  therefore  probably  of  very  different  constitution  in 
the  lymph-spaces  of  the  various  tissues.  The  analysis  of 
lymph  taken  from  the  large  lymphatics  cannot  give  us  any 
information  as  to  the  composition  of  the  tissue-fluids  them- 
selves. 

For  those  who  wish  to  maintain  the  old  theory  of  diffusion 
and  to  consider  the  capillary  wall  as  a  dead  membrane  passively 
concerned  in  the  operation,  the  cells  may  be  regarded  as  taking 
from  the  lymph  the  special  substances  which  they  need,  con- 
verting them  into  an  insoluble  or  colloid  combination,  which 
has  thus  lost  all  power  of  diffusion,  e.  g.,  sugar  into  glycogen  or 
fat,  the  soluble  into  insoluble  compounds  of  lime.  In  this  way 
the  special  substance  would  become  less  concentrated  in  the 
lymph  than  in  the  plasma,  and  a  fresh  supply  would  be  con- 
tinually passing  according  to  the  laws  of  diffusion  through 
the  capillary  walls  from  the  blood  into  the  lymph,  without  the 
simultaneous  passage  of  water.  But  there  is  really  no  reason 
for  refusing  to  the  capillary  walls  of  the  endothelial  cells  the 
'  active '  functions  which  it  is  allowed  are  involved  in  the  case 
of  all  other  cells.  However  this  may  be,  the  old  idea  of  the 
plasma  stream  ^  must  be  relinquished. 

Impossible  as  it  is  for  the  food-stuffs  to  be  conveyed  to  the 
various  cells  by  a  stream  of  plasma  common  to  all  alike,  so  it  is 
equally  impracticable  for  the  end-products  of  metabolism  to  be 
returned  by  the  common  lymph  stream  to  the  blood.  We 
must  rather  assume  that  these  final  products  penetrate  through 
the  neighboring  lymph-spaces  into  the  nearest  capillaries. 

The  most  important  of  these  waste  materials,  carbonic  acid, 
•can  be  proved  to  make  its  exit  in  this  manner.  The  tension  of 
■CO2  is  less  in  the  large  lymph-trunks  than  in  the  blood  (compare 
Lecture  XVIII.) .  Moreover  the  lymph-flow  is  much  too  slow 
to  carry  off  the  large  amounts  of  carbonic  acid  quickly  enough. 
The  passage  of  800  to  1000  grms.  of  this  gas  through  these 
organs  in  the  twenty-four  hours  could  not  be  effected  unless 
the  CO2  were  conveyed  directly  into  the  circulation.  And  this 
is  probably  the  case  with  urea  and  the  other  end-products  of 
metabolism.     We   must   assume  that    these   latter   reach   the 

^  [J.  e.,  the  irrigation  theory  of  Bartliolini.] 


222  LECTURE    XV 

blood  directly  through  the  capillary  walls  and  not  through  the 
medium  of  the  lymph. 

We  have  now  to  ask  :  What  are  the  functions  of  the  lymph  ? 
What  are  the  objects  of  the  lymph-spaces?  Might  not  the 
interchange  of  material  proceed  in  all  the  other  organs  as  it 
does  in  the  glomeruli  of  the  kidney  ? 

In  the  first  place,  the  lymph-spaces  have  a  purely  mechanical 
use,  inasmuch  as  they  enable  the  blood-vessels  to  alter  their 
lumen  and  so  regulate  their  pressure.  Were  the  blood-vessels 
surrounded  with  rigid  tissue,  this  would  be  impossible.  They 
need  to  be  set  in  a  compressible  medium,  which  can  adjust 
itself  to  the  variations  of  the  vascular  lumina.  Secondly, 
supposing  that  every  cell  were  in  immediate  contact  with  a 
capillary  vessel,  as  in  the  Malpighian  glomerulus,  the  capillary 
system  would  become  so  enlarged  that  the  circulation  of  the 
blood  would  become  too  much  slowed  down. 

These  considerations  however  refer  to  the  uses  of  the 
lymph-spaces  only,  and  not  to  those  of  the  larger  lymphatics. 
They  do  not  explain  why  the  fluid  collects  from  the  lymph- 
spaces  into  larger  and  larger  vessels,  which  finally  empty 
themselves  into  the  blood-stream.  Could  not  the  food-stuffs 
pass  through  the  capillary  wall  of  the  blood-vessels  straight 
into  the  lymph-spaces,  and,  conversely,  could  not  the  final 
products  of  metabolism  find  their  way  directly  from  the  lymph- 
spaces  through  the  capillary  wall  into  the  blood  ?  What  is  the 
need  for  a  special  stream  of  lymph  ? 

In  answering  this  question  we  have  an  indication  in  the 
fact  that  in  the  course  of  the  lymphatics  are  interposed  lym- 
phatic glands,  in  which  the  lymph-cells  are  being  continually 
formed  by  division. 

We  do  not  yet  know  very  much  of  a  definite  character 
concerning  the  cells  of  the  lymph,  the  leucocytes ;  although 
they  undoubtedly  are  of  great  importance  in  the  animal  economy. 
We  know  that  they  can  make  their  way  out  through  the 
capillary  wall  and  wander  among  the  tissues.  They  may  be 
seen  assembling  in  masses  wherever  injurious  substances  are 
formed,  where  foreign  bodies,  poisonous  matters,  or  micro- 
organisms penetrate  the  tissues,  as  well  as  in  cases  of  inflam- 
mation and  all  kinds  of  pathological  processes  which  accompany 
the  degeneration  of  tissue.  It  appears  that  their  function  is  to 
clear  away  the  products  of  tissue-disintegration  ^  and  to  render 
noxious   substances   harmless.     They  may  be   seen    enclosing 

1  An  account  of  the  literature  on  the  behavior  of  leucocytes  under  normal 
and  pathological  conditions  is  given  in  the  monograph  of  Herm.  Rieder,  "  Beitr. 
z.  Kenntniss  der  Leucocytose."    Leipzig,  Vogel :  1892. 


LYMPH  223 

within  their  protoplasm  solid  particles,  or  invading  micro- 
organisms ;  ^  'and  it  is  probable  that  they  also  take  up  and  alter 
substances  in  a  fluid  and  dissolved  condition.  I  have  already 
mentioned  the  part  which  has  been  ascribed  to  them  in  the  ab- 
sorption of  proteid,  in  the  regeneration  of  peptone  into  proteid 
within  the  intestinal  wall,  and  in  the  conveyance  of  the  peptone 
which  reaches  the  blood  in  this  form. 

Now  there  is  a  constant  disintegration  of  lymph-cells 
going  on.  We  know,  for  instance,  from  Stöhr's  experiments  ^ 
that  leucocytes  emigrate  in  masses  through  the  epithelium 
from  the  adenoid  tissue  of  the  tonsils  and  of  the  follicles  of  the 
tongue,  as  well  as  from  the  follicles  of  the  whole  intestinal  and 
bronchial  mucous  membranes.  Stöhr  considers  that  an  expul- 
sion of  "  used-up  material "  is  involved.  These  leucocytes 
must  be  replaced  by  the  formation  of  new  ones  in  the  lymph- 
glands  and  by  a  supply  of  young  cells  passing  with  the  lymph 
into  the  blood. 

Finally  the  lymph-glands  may  have  the  function  of  altering 
the  various  kinds  of  lymph  which  flow  into  them  from  all 
the  tissues,  so  as  to  assimilate  it  to  the  plasma  before  it  enters 
the  circulation.  Without  such  previous  assimilation  a  fluid, 
which  had  been  changed  by  the  processes  of  metabolism  in  the 
tissues,  might  either  disintegrate  the  blood-corpuscles  when  it 
passes  into  the  blood-stream  or  do  mischief  in  some  other  direc- 
tion. 

It  is  known  that  injurious  substances  of  all  kinds,  as  w^U  as 
microorganisms,  are  detained  in  the  lymph-glands  so  that  they 
cannot  enter  the  blood,  there  to  be  passed  on  to  the  tissues. 
With  this  fact  is  also  connected  the  swelling  of  the  lymph- 
glands  as  a  result  of  infection. 

In  the  following  table  I  append  some  of  the  most 
reliable   analyses  as  examples  of  the  composition   of  lymph. 

'  It  is  well  known  that  El.  MetchnikofF  was  the  first  author  to  introduce  the 
view  that  the  leucocytes  wage  war  against  the  intruding  microorganisms  and 
other  injurious  and  foreign  substances — the  so-called  doctrine  of  phagocytosis. 
Arb.  a.  d.  Zoolog.  Inst,  zu  Wien,  vol.  v.  Hft.  ii. :  1883  ;  Biolog.  Centralbl.,  vol.  lii.: 
1883-1884;  Virchow's  Arch.,  vol.  xcvi.  p.  177:  1884;  vol.  xcvii.  p.  502:  1884; 
vol.  cvii.  p.  209:  1887;  vol.  cix.  p.  176 :  1887;  vol.  cxiii.  p.  63 :  1888:  Annales 
de  rinstiua  Pasteur,  p.  321:  1887;  p.  604:  1888.  [See  also  his  work,  "The 
Pathology  of  Inflammation,"  Paris,  1892,  translated  by  E.  H.  Starling. 
London,  Kegan  Paul  &  Co.,  1893.]  This  doctrine  has  been  the  subject  of  much 
dispute.  Compare  Baumgarten,  Berlin.  Min.  Wochenschr., -p.  SIS  :  1884;  and 
Centralbl.  f.  klin.  3Ied., 'No.  26  :  1888;  and  Weigert,  i^oj-i'scA?-.  d.  Med.,  p.  732: 
1887 ;  and  p.  83  :  1888.  On  the  other  hand  a  highly  interesting  observation, 
which  bears  out  Metchnikoff^s  theoi-y,  has  been  recently  published  by  Vaillard  & 
Vincent :  Annales  de  l' Institut  Pasteur,  Annee  5,  p.  34 :  1891. 

2  Ph.  Stöhr,  Biolog.  Centralbl.,  \ol.  ii.  p.  368  :  1882  ;  Sitzungsber.  d.  physik. 
med.  Ges.  zu  Würzburg,  May  19,  1883  ;  Virchow's  Arch.,  vol.  xcvii.  p.  211 : 
1884. 


224  LECTURE    XV 

To  these  I  have  added  a  few  analyses  of  the  '  pathological 
transudations/  ascitic  fluid,  pleural  and  pericardial  effusions, 
dropsical  fluid,  and  hydrocele  fluid,  which  are  considered  by 
most  authors  as  lymph  increased  above  the  normal  by  patho- 
logical conditions  and  obstructed  absorption.  Even  the  fluid 
contained  in  the  ventricles  of  the  brain,  which  it  is  well  known 
may  be  increased  largely  in  disease  (e.  ^.,  hydrocephalus),  is 
regarded  as  lymph  by  many  authors  because  the  ventricles  of 
the  brain  communicate  by  means  of  the  foramen  of  Magendie 
with  the  lymph-spaces  of  the  subarachnoid  tissue.  Some  ob- 
servers however  deny  that  this  communication  exists.  It  must 
also  be  remembered  that  the  ventricles  of  the  brain  are  covered 
with  epithelium,  and  that  the  fluid  in  them  might  be  a  specific 
secretion  of  these  cells.  The  cerebro-spinal  fluid  is  not  spon- 
taneously coagulable. 

Finally,  I  have  included  a  few  analyses  of  chyle  in  Table 
I.  I  have  already  shown  that  the  chyle  of  fasting  animals 
is  nothing  but  lymph,  and  that  fat  droplets  are  mixed  with 
this  lymph  only  during  the  digestion  of  fatty  food  (Lecture 
XIIL). 

I.  C.  Schmidt,  "Charakteristik  der  epidemischen  Cholera."  Mitau  u. 
Leipzig,  p.  29  :  1850.  II.  and  III.  Gubler  &  Quevenne,  Gaz.  Med.  de  Paris, 
Nos.  24,  27,  30,  and  34:  1854.  The  different  specimens  of  lymph  were  obtained 
■by  pricking  the  varicose  enlargements  of  the  lymph-vessels  in  the  skin  of  a 
woman's  thigh.  As  the  woman,  with  the  exception  of  this  lymph  obstruction, 
was  otherwise  in  a  normal  condition,  we  may  jjerhaps  regard  this  as  ordinary 
lymph.  IV.  Eees,  Phil.  Trans.,  p.  81 :  1892.  V.  Hoppe-Seyler,  "  Physiol. 
Chem.,"  Berlin,  Hirschwald,  p.  597  :  1881.  Effusion  of  chyle  into  the  peritoneal 
cavity  in  consequence  of  rupture  of  the  chyle-vessel.  The  chyle  was  obtained  by 
tapping  the  abdomen.  Hoppe-Seyler  thought  that  it  was  undoubtedly  normal 
•chyle.  VI.  C.  Schmidt,  ^oc.  cii.,  p.  140.  VII.  and  VIII.  Hoppe-Seyler,  ^oc.  ci<. , 
p.  505.  IX. -XI.  Herm.  Nasse,  "  Ueb.  Lymphe  u.  deren  Bildung,"  Akad. 
Gelegenheitschr.,  Marburg,  1872.  XII.  C.  Schmidt,  loc.  cit,,  p.  138.  Taken 
from  the  same  dog  from  which  the  blood  for  Analysis  VI.  was  drawn.  XIII.- 
XVII.  C.  Schmidt,  Bulletin  de  St.  Petersbourg,  vol.  iv.  p.  355  :  1861. 

I. -III.  V.  Hensen  and  C.  Dähnhardt,  Virchow's  Arch.,  vol.  xxxvii.  p.  55  : 
1866.  Both  legs  of  the  patient  were  swollen  from  the  extensive  thickening  of 
the  subcutaneous  tissue  and  corium  ;  heart  failure  and  ascites  were  also  present. 
IV.-VI.  Hoppe-Seyler,  Virchow's  Arch.,  vol.  ix.  p.  250:  1856.  VII.  Gorup- 
Besanez,  "  Lehrb.  d.  physiol.  Chem.,"  3d  edit.,  p.  415.  Braunschweig,  Vieweg 
and  Sohn,  1874.     VIII.  Wachsmuth,   Virchow's  Arch.,  vol.  vii.  p.  334 :  1855. 

IX.  Hoppe-Seyler,    "  Physiolog.   Chem.,"   Berlin,   Hirschwald,   p.   605:   1881. 

X.  Scherer,   Verhandl.  d.  med.  phys.  Ges.  zu    Würzburg,  vol.  vii.  p.  268  :  1857. 

XI.  Hammarsten,  Upsala  Läkareförenings  For  handling  a,r,  vol.  xiv.  p.  33  :  1878. 
XII. -XV.  C.  Schmidt,  "  Charakteristik  d.  epidem.  Cholera,"  Leipzig  u.  Mitau, 
pp.  122  and  123 :  1850.  XVI.-XVIII.  Hoppe-Seyler,  Virchow's  Arch.,  vol.  ix. 
p.  250 :  1856. 

I.-V.  Hoppe-Seyler,  Virchow's  Arch.,  vol.  xvi.  p.  391 :  1859.  VI.  and  VII. 
Halliburton,  Journ.  of  Physiol.,  vol.  x.  pp.  233  and  234  :  1890.  VIII.  and  IX. 
•C.  Schmidt,  "  Charakteristik  de  epidem.  Cholera,"  Leipzig  and  Mitau,  pp.  135- 
138:  1850.  X.  C.  Schmidt,  loc.  cit.,  p.  136.  "Fluid  between  the  dura  mater 
and  the  vault  of  the  skull,  which  was  greatly  expanded."  XI.  Hoppe-Seyler, 
loc.  cit. 


LYMPH 


225 


W 


XI 


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15 


226 


LECTURE    XV 


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From  one  and  the  same 
subject. 

Hoppk-Seyler. 

982.2 
17.8 

3.6 
9.0 

1-5 
1— ( 

> 

X 

|E9no;iJ8tj 

967.7 
32.3 

16.1 

H-5 

> 
X 

•DorjEpnsnBJx 
IBinaiji 

957.6 
42.4 

27.8 

kJ  1       'mB-ia 

^     JO  s8iOTi;n9A 
?<(       rao^  ptnij 

o 

a 

983.5 
16.5 

8.0 

8.5 

^     gqij  JO  sragpa 

From  one  and  the  s 
subject. 

C.  Schmidt. 

988.7 
11.3 

3.6 

7.7 

1—! 
1— I 
1— 1 

X! 

•aoiiBpnsnBix 
IBauoiiaea: 

978.9 
21.1 

11.3 

9.8 

M     •noii'BpnsuBJX 

964.0 
36.0 

■  28.5 

7.6 

'                  '                     1 

1— i 

X 
X 

Hydrocele. 

•sasÄiBny           cs-icotj^,       oeoSo,     , 
U  JO  UBajij          cä^öcrI       -^cicdr^i     1 
■naxsavKKVH       co  co      ^ 

Ol 

•aaaanos 
Xq  sisXi'Bnv' 

!>:  W  O'^     1          051>     1      1      1      1 
1C-*         CO     '                         1      1      1      1 

G5 

X 

t— 1 

hH 

1— 1 

1— I 
> 

Liquor  Pericardii. 

•aaiias 
-aadOH 

961.8 
38.2 

24.6 

•HIQHSHOT^ 

962.5 
37.5 

22.8 

•zasvsaa 

-diiaoo 

^q  stsiiBOV 

IC  Tj^  Ö  -^  C4          1    CO     1      1      i      1 
IC  •*         C<1  I-l           1             1      1      1      1 
G5 

> 
> 
> 

h-{ 

Peritoneal  Trans- 
udation in  a  case  of 
Cirrhosis  of  the  Liver. 
Hoppe-Sevleb. 

•qjB9(I  J9JJY 

983.3 
16.7 

61.1 

8.2 

•SniddBX 

pn'039g 

982.5 
17.5 

7.7 
8.1 

•SniddBX 

984.5 
15.5 

6.2 

8.5 

h- 1 

I-H 

HH 
1-5 

Human  Lymph  from  a 
Fistula  ig  the  Thigh. 

Hensen  and 

DÄUNHARDT. 

985.2 
14.8 

986.1 
13.9 

CO      ic  t^  o  CO 
t>  CO    CO    CO      o  ■*  T-i  ic  ic  1-1 
i>--(r4    (N    rH      öodcdööö 

00  -H    _>^_ 

Ol 

Water  .    .    . 
Dried  subst. 
Fibrin   .    .    . 
Proteid 
Extractives . 
Fat,  lecithin, 
Cholesterin 
Ash   .... 
NaCl     .    .    . 

CaO  .... 

LYMPH 


227 


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228  LECTURE   XV 

From  these  tables  it  may  be  seen  that  the  lymph  drawn 
from  different  parts  of  the  body  is  highly  variable  in  its 
composition,  and  especially  as  regards  its  proportion  of  proteid. 
This  is  also  the  case  with  the  pathological  transudations.  The 
amoimt  of  proteid  varies  between  0.3  and  4.9  per  cent.  The 
quantity  of  fibrin  is  always  less  than  in  the  blood ;  it  varies  in 
the  lymph  between  0.04  and  .02  per  cent.,  in  the  blood  between 
0.2  and  0.4  per  cent. 

The  proportion  of  the  two  kinds  of  proteid,  the  globulins 
and  the  albumins,  varies  in  the  lymph  between  as  wide  limits 
as  they  do  in  the  blood-plasma  (compare  Lecture  XIV.). 
Experiments  made  so  far  on  this  subject  have  given  the 
noteworthy  results^  that  if  blood,  lymph,  and  chyle,  or  blood 
and  a  pathological  transudation  be  taken  from  one  and  the 
same  individual,  these  two  kinds  of  proteid  are  nearly  always 
present  in  the  same  proportion  in  the  transudations  and  in  the 
lymph,  however  great  the  difference  may  be  in  the  total  amount 
of  proteid. 

We  cannot,  within  the  scope  of  this  book,  treat  of  the 
causes  and  mode  of  formation  of  the  pathological  transudations. 
We  know  that  nerve  fibers  run  to  every  single  endothelial  cell 
of  the  capillary  wall,  and  that  therefore  disturbances  in  the 
innervation  of  the  capillary  wall  may  be  reflexly  transmitted 
from  any  organ  to  any  other  organ.  We  must  likewise 
remember  that  every  mechanical  disturbance  of  the  circulation 
and  every  change  in  the  chemical  composition  of  the  blood 
interfere  with  the  normal  nutrition  of  the  capillary  wall  and 
lower  the  power  of  resistance  possessed  by  the  endothelial  cells, 
so  that  they  are  not  so  capable  of  preventing  the  escape  of 
constituents  of  the  blood-plasma.  Finally,  we  must  not  forget 
that  abnormal  constituents  of  all  kinds  act  directly  as  irritants 
on  the  endothelial  cells  of  the  capillary  wall,  so  soon  as  they 
enter  the  blood,  and  may  thus  alter  their  functions.  The  cause 
of  the  formation  of  transudations,  which  have  been  patholog- 
ically increased  and  altered,  may  therefore  be  of  a  very  vary- 
ing character  in  different  organs.  Their  study  must  for  the 
present  be  left  to  the  domain  of  special  pathology,  where  the 
results  so  far  attained  in  physiological  experiment  may  be 
utilized.  A  critical  account  of  the  physiology  of  lymph  may 
be  found  in  the  work  of  Heidenhain  already  referred  to. 

^G.  Salvioli,  Du  Bois'  Arch.,  p.  268:  1881 ;  F.  A.  Hoffmann,  Arch.  f.  exp. 
Path.  u.  Pharm.,  vol.  xvi.  p.  133 :  1882. 


LECTURE   XVI 


THE    SPLEEN 


Before  leaving  the  subject  of  lymph  and  the  lymphatic 
glands,  we  will  take  for  our  consideration  another  organ  which 
is  supposed  to  have  similar  functions,  viz.,  the  spleen. 

With  the  single  exception  of  the  amphioxus,  the  spleen  is 
invariably  present  in  all  vertebrates,  and  is  in  all  cases  of  very 
similar  structure. 

There  is  however  an  essential  difference  between  the  spleen 
and  the  lymphatic  glands,  in  that  the  leucocytes  formed  in  the 
spleen  enter  directly  into  the  blood-stream.  The  blood  of  the 
splenic  vein  contains  more  leucocytes  than  the  arterial  blood. 
This  was  shown  by  Kölliker  and  Hirt,^  whose  experiments 
were  afterwards  confirmed  by  numerous  observers.^  In  his 
investigations  on  the  metabolism  of  Rhine  salmon  (vide  p.  79), 
Miescher^  carried  out  a  number  of  very  careful  estimates  on 
this  point,  the  average  number  of  white  corpuscles  to  every  100 
red  blood-corpuscles  being 

Cardiac  Blood.  Splenic  Blood. 

1.79  1.79  8.31  7.1  white  corpuscles. 

The  earliest  investigations  on  the  functions  of  this  organ  dealt 
v/ith  the  effects  of  its  extirpation.  Even  Pliny  *  mentions  as 
well  known  the  fact  that  dogs  will  survive  the  extirpation  of 
the  spleen.  Since  that  time  occasional  extirpations  of  the 
spleen  have  been  successfully  performed  on  diiferent  animals.® 
But  it    is    only  since    the    aseptic    treatment   of  wounds  has 

■^  Hirt,  "  De  copia  relat.  corpusc.  sanguin.  alb.,"  Dissert.  Leipzig  :  1855. 

2  P.  Emelianow,  Arch.  d.  Sciences  biolog.,  St.  Petersbourg,  vol.  ii.  p.  145  : 
1893.    The  earlier  literature  is  here  quoted. 

3  Miescher,  Du  Bois'  Arch.,  Anat.  Abth.,  p.  212  :  1881. 
*  Plinius,  "Histor.  naturalis.,"  lib.  xi.  c.  xxxvii. 

^  An  account  of  the  earliest  literature  on  extirpations  of  the  spleen  is  given 
by  G.  Adelmann,  Deutsche  Klinik,  p.  183  :  1856. 

229 


230  LECTUEE    XYI 

been  introduced  that  these  operations  have  formed  the  bases 
of  systematic  series  of  experiments.  Among  the  latest  re- 
searches of  this  nature  we  may  mention  the  following  :  Guido 
Tizzoni  ^  cut  out  the  spleen  in  eighteen  rabbits,  young  and 
old.  The  longest  time  during  which  the  animal  was  under 
observation  was  240  days.  He  could  discover  no  ill  effects 
from  the  operation.  In  the  young  animals  the  growth 
proceeded  as  usual,  and  in  adults  the  sexual  fimctions  were 
undisturbed  and  healthy  offspring  were  produced.  In  the 
same  way,  Konrlow^  found  that  gumea-pigs  bear  extirpa- 
tion of  the  spleen  well,  and  that  they  grow  and  propagate 
like  normal  animals.  A.  Dastre^  cut  out  the  spleen  in  young 
dogs,  cats,  rats,  and  guinea-pigs,  and  compared  their  rate  of 
growth  with  that  of  normal  animals  from  the  same  litter. 
He  could  discover  no  difference.  Unfortunately  the  obser- 
vation lasted  but  a  short  time — only  four  months  in  the  case 
of  the  cats,  and  until  they  were  full-grown  in  the  case  of  the 
guinea-pigs. 

The  question  now  arises  as  to  whether,  if  the  animals  sur- 
vive the  removal  of  their  spleen,  changes  may  not  occur  in  one 
or  other  of  their  functions.  Alterations  in  blood  formation 
were  especially  anticipated.  Of  the  numerous  experiments 
made  in  this  connection  may  be  mentioned  the  most  recent. 
P.  Emelianow  ^  found  that,  after  extirpation  of  the  spleen  in 
dogs,  the  number  of  red  blood-corpuscles  diminished,  while 
that  of  the  white  was  increased.  O.  Vulpius,^  experiment- 
ing on  rabbits  and  goats,  also  observed  that,  when  the  spleen 
was  excised,  the  red  blood-corpuscles  decreased  by  not  more 
than  20  per  cent.,  but  that  this  diminution  was  made  up  after 
about  a  month  had  elapsed.  The  number  of  white  blood- 
corpuscles  immediately  after  the  operation  rose  to  double 
the  normal,  the  increase  however  lasting  at  the  most  nine 
weeks. 

From  this  increase  of  white  and  diminution  of  red  blood- 
corpuscles  it    is  natural    to  conclude  that    in    the  spleen    the 

^  G.  Tizzoni,  Archivio  per  It  scienze  mediche,  vol.  viii.  No.  13,  p.  255.  Sum- 
marized in  Arch.  ital.  d.  Biol.,  vol.  vi.  p.  103 :  1884. 

^Kourlow,  Vratsch,  Nos.  23,  24,  1889;  No.  19,  1892  (Russian). 

*  A.  Dastre,  Comptes  rend.  Soc.  Biol.,  p.  584:  1893  ;  and  Arch.  d.  Physiol., 
July,  1893. 

■*P.  Emelianow,  Arch.  d.  Sciences  bioL,  St.  P^tersbourg,  vol.  ii.  p.  157:  1893. 
The  earlier  literature  is  here  quoted. 

^O.  Vulpius,  Beitr.  z.  klin.  Chir.,  vol.  xi.  p.  684:  1894.  This  author  gives 
a  summary  of  the  earlier  and  very  abundant  literature  on  the  infiuenee  of  ex- 
cision of  the  spleen  on  the  amount  of  red  and  white  blood-corpuscles.  There  is 
also  an  account  on  pages  687  and  688  of  the  numbers  of  blood-corpuscles  in  man 
after  extiri^ation  of  the  spleen. 


THE    SPLEEX  231 

red  are  formed  from  the  white  corpuscles.  Moreover  some 
observers  "have  described  in  the  splenic  pulp  nucleated  red 
blood-corpuscles  similar  to  those  in  embryonic  tissue.  It 
might  be  assumed  that  these  nucleated  red  blood-corpuscles 
formed  the  intermediate  steps  in  the  conversion  of  white  into 
the  non-nucleated  red  corpuscles.  ]Miescher's  observation  ^  that 
the  spleen  is  richer  in  hemoglobin  than  the  blood  deserves  our 
notice.  This  author,  adopting  Hüfner's  method,  found  that  the 
salmon  had  twice  as  much  hemoglobin  in  the  spleen  as  in  the 
blood. 

We  have  now  to  consider  whether  the  transitory  character 
of  the  disturbances  in  the  blood  formation,  which  appear  after 
excision  of  the  spleen,  may  not  be  accounted  for  by  the  fact 
that  other  organs  of  the  body  may  take  up  the  splenic  functions. 
It  is  often  stated  that  the  lymphatic  glands  swell  after  removal 
of  the  spleen.  This  is  however  by  no  means  a  constant  phenom- 
enon, and  was  absent,  for  example,  in  a  number  of  experi- 
ments of  this  description  carried  out  by  Vulpius  ^  in  rabbits  and 
goats.  Swelling  of  the  lymphatic  glands  has  often  been 
observed  in  man  as  a  result  of  excision  of  the  spleen.  In 
this  case  however  it  is  doubtful  whether  this  change  should 
rather  be  ascribed  to  the  disease  which  necessitated  the 
operation. 

It  seems  to  me  more  probable  that  the  duties  of  the  spleen 
are  fulfilled  by  another  tissue,  viz.,  the  red  marrow  of  bones. 
In  1869  Xeumann  ^  and  Bizzozero  *  showed  that  the  red  marrow 
of  the  flat  bones,  the  bodies  of  the  vertebrse,  and  the  proximal 
epiphyses  of  the  bones  of  the  limbs  in  mammals  contained 
nucleated  cells  tinged  with  hemoglobin,  resemblmg  in  every 
respect  embryonic  red  blood-corpuscles.  It  is  thought  that  these 
cells  are  formed  from  leucocytes  and,  multiplying  by  cell-division, 
are  converted  into  non-nucleated  red  blood  discs.  The  red  bone- 
marrow  presents  one  striking  similarity  to  the  splenic  tissue, 
in  that  the  veins  appear  to  lose  their  proper  wall,  thus  allow- 
ing the  blood  to  come  into  immediate  contact  with  the  tissue- 
cells.^  It  seems  tlierefore  a  likely  hypothesis  that  the  red 
bone-marrow  should  be  able  to  take  up  the  functions  of  the 

iMiescher,  Du  Bois'  Arch.,  Aiiat.  Abth.,  p.  212  :  1881. 

2  Vulpius,  loc.  cit.,  p.  694,  contains  full  references  to  previous  work  on  the 
subject. 

*E.  Neumann,  Arch.  d.  Heilkunde,  Jahrgang  x.  p.  68:  1869;  Yirchow's 
Arch.,  vol.  cxis.  p.  385  :  1890. 

^  Bizzozero,  "  Sul  midollo  delle  ossa,"  Kapoli :  1869. 

5  Hover,  3Ied.  Centralbl.,  Nos.  16  and  17:  1869;  G.  E.  Eindfleisch,  Arch.  f. 
mikr.  Anat.,  vol.  vii.  p.  1  :  1880. 


232  LECTURE    XVI 

spleen  when  this  organ  was  removed.  Thus  P.  Emelianow^ 
foimd  in  the  red  marrow,  after  extirpation  of  the  spleen  in 
dogs,  an  increase  of  leucocytes  containing  hemoglobin,  as  well 
as  of  the  transition-forms  between  these  and  the  red  blood- 
corpuscles.  The  observations  of  Pouchet  ^  show  however  that 
the  harmlessness  of  this  operation  does  not  depend  on  changes 
in  the  red  marrow,  since  the  spleen  may  be  removed  in  the 
fish  which  have  no  bone-marrow  without  causing  any  alteration 
in  the  composition  of  their  blood. 

A  number  of  cases  are  on  record  in  which  the  spleen  has 
been  excised  in  man.  In  some  instances  this  was  rendered 
necessary  by  the  prolapse  of  the  organ  through  a  wound  in  the 
abdominal  wall.  Many  such  cases  have  recovered  even  in  the 
pre-antiseptic  days.  Morgagni^  records  the  case  of  a  woman 
in  whom  a  prolapsed  spleen  was  removed,  and  who  lived  for 
five  years  afterwards  and  bore  children.  In  1678  a  Colburg 
surgeon,  Nicolaus  Matthia,  extirpated  the  spleen  of  a  young 
man  which  had  prolapsed  in  consequence  of  a  dagger  wound 
of  the  abdomen.  The  patient  lived  at  least  six  years  after  the 
operation,  went  about  his  ordinary  occupations,  and  begat 
children.* 

Encouraged  by  these  results,  surgeons  have  tried  the  effect 
of  excising  spleens  in  diseased  conditions,  such  as  hypertrophy, 
sarcoma,  hydatid  cysts,  floating  spleen,  etc.  In  the  days 
before  asepsis  and  antisepsis  were  practiced,  a  violent  dispute 
arose  as  to  whether  such  a  bold  operation  was  justifiable.  We 
may  refer  our  readers  to  the  treatises,  which  appeared  in  1855 
on  the  occasion  of  Küchler's  operation.^  This  surgeon  had 
ventured  to  remove  a  spleen  in  a  man  suffering  from  hyper- 
trophy in  consequence  of  malaria,  and  had  lost  his  patient. 
On  this  account  he  was  violently  attacked  by  many  of  his 
colleagues  and  especially  by  Gustav  Simon, ^  a  surgeon  in 
Heidelberg ;  and  as  vigorously  defended  by  G.  Adelmann,^  a 

1  p.  Emelianow,  Arch.  d.  Sciences  biolog.,  St.  Petersbourg,  vol.  ii.  p.  135 : 
1893.    The  earlier  literature  is  here  quoted. 

2  Pouchet,  Gaz.  med.  d.  Paris,  p.  316  :  1878. 

^Morgagni,  "De  sedibus  et  caus.  morbor,"  lib.  v.  epist.  65,  art.  10,  p.  368: 
Patavii,  1765. 

*  "  Ephemerides  Medic.  Physic.  Natur.  Curiosor,"  Decuria  ii.  Ann.  ii.  (1684), 
p.  378  :  Norimb.  1685. 

^H.  Küchler,  "  Exstirpation  eines  Milztumors;  wissenschaftliche  Beleuch- 
tung der  Frage  über  Exstirpation  der  Milz  bei  dem  Menschen,"  &c.,  Darmstadt : 
1855. 

"  G.  Simon,  "Die  Exstirpation  der  Milz  am  Menschen  nach  dem  jetzigen 
Standpunkte  der  Wissenschaft  beurtheilt,"  Giessen  :  1857. 

'  G.  Adelmann,  Bemerkungen  zu  Dr.  Küchler's  Schrift :  "  Exstirpation  eines 
Milztumors,"  Deutsche  Klinik,  Nos.  17  and  18,  pp.  175  and  183 :  1856,  contains  a 
critical  account  of  all  the  earlier  works  on  the  extirpation  of  the  spleen. 


THE    SPLEEN  233 

surgeon  of  Dorpat.  Since  aseptic  precautions  have  been 
brought  to'  perfection,  removal  of  the  spleen  has  become  much 
more  frequent  and  has  been  attended  with  more  and  more 
favorable  results.  In  those  cases  which  do  not  succeed  the 
failure  should  probably  hardly  ever  be  ascribed  to  the  loss  of 
the  splenic  function.  Of  course  in  such  operations  it  is  difficult 
to  say  whether  death,  if  it  ensues,  is  due  to  the  consequences  of 
the  disease  or  to  the  absence  of  the  organ.  In  the  cases  which 
survive  the  operation  unfortunately  no  record  is  usually  kept  of 
the  length  of  the  subsequent  life.  In  1876  however,  P6an^ 
showed  a  woman  at  the  Parisian  Academic  de  M^decine  M^hose 
spleen  had  been  excised  ten  years  previously,  in  consequence 
of  cystic  degeneration,  and  who  had  remained  throughout  that 
time  in  excellent  health.  Vulpius  ^  records  the  case  from 
Czerny's  clinique  in  Heidelberg  of  a  woman  in  whom  a  hyper- 
trophied  floating  spleen  was  extirpated.  The  patient  recovered 
slowly,  apparently  because,  in  addition  to  hypertrophy,  she 
suffered  from  severe  nervous  troubles  and  attacks  of  hys- 
teria. Fifteen  years  after  the  operation  however,  she  still 
enjoyed  moderately  good  health.  The  nervous  symptoms  had 
abated,  and  the  blooming  color  on  her  cheeks  showed  that  there 
was  no  disturbance  in  her  blood  formation.  In  the  first 
few  years  after  the  operation  there  had  been  some  swelling 
of  the  inguinal  and  cervical  glands,  but  this  had  gradually  dis- 
appeared. 

In  certain  cases  of  enlarged  spleen,  such  as  leukemia  and 
lardaceous  disease,  other  organs — liver,  lymphatic  glands, 
kidneys — are  usually  affected  at  the  same  time ;  and  therefore 
no  cure  can  result  from  removal  of  the  spleen.  Idiopathic 
tumors  of  the  spleen  rarely  occur,  but  here  again  the  blood  is 
in  an  abnormal  condition,  as  shown  by  the  existence  of  anemia, 
leucocytosis,  etc.  Better  results  might  be  anticipated  from  this 
operation  in  cystic  disease,  e.  g.,  hydatids,  but  here  a  partial 
resection  is  usually  sufficient.  Extirpation  is  also  indicated  in 
cases  of  floating  spleen,  where  this  organ,  especially  if  it  be 
hypertrophied,  sinks  occasionally  into  the  pelvis  and  produces 
painful  stretching  of  the  duodenum  and  stomach,  strangu- 
lation of  the  blood-vessels,  disturbances  in  digestion  and  nutri- 
tion, &c. 

In  1893  A.  Dandolo  ^  collected  all  the  cases  in  which  ex- 
cision of  the  spleen  had  been  performed. 

1  Pean,  Bulletin  de  VAcacl.  de  Med.,  No.  29  :  1876. 

2  Vulpius,  Beitr.  z.  klin.  Chir..  toI.  xi.,  pp.  638-641 :  1894. 
^  Dandolo,  Gazs.  med.  lombarda,  Nos.  7-9  :  1893. 


234 


LECTURE    XVI 


Cases. 


Cure. 


Death. 


Floating  spleen 

Suppuration 

Simple  cysts   .    .  .    .    .    . 

Hydatid  cysts 

Amyloid  spleen 

Fibroma  ...        

Sai'coma 

Lympho-sarcoma  .  .    . 

Venous  engorgement. 
Simple  hypertrophy  .  .    .    . 

Malarial  hypertrophy  .    . 
Leukemia  and  pseudo-leukemia 


17 

2 

4 

4 

1 

1 

2 

2 

3 

18 

23 

25 


102 


15 
2 
4 
3 


1 

2 

7 
12 


1 
1 
1 
1 

3 
11 
11 

25 


56 


In  1894  O.  Yulpius^  published  a  list  of  117  extirpations, 
50.4  per  cent,  of  which  resulted  in  cure,  49.6  in  death. 


Cases. 

Cure. 

Death. 

Leukemia   . 

Simple    and    malarial 

and  floating  spleen 
Hydatid      .         ... 
Simple  cysts  .... 

hypertrop 

hy 

28 

66 
5 
4 
4 
3 
3 
1 
1 
2 

32 

42 
3 
4 
3 
3 

1 

25 

24 
2 

Sarcoma 

Suppuration   .... 
Venous  congestion    . 
Amyloid  .                .    . 

1 

3 
1 

Syphilis  .            ... 

Kupture  .... 

2 

117 

59  (50.4%) 

58  (49.6%) 

As  regards  the  operations  for  enlargement  of  the  spleen  in 
leukemia,  again  only  one  is  reported  by  Vulpius  to  have 
resulted  in  a  permanent  cure,  and  even  in  this  case  there  was 
some  doubt  as  to  the  diagnosis.  If  we  deduct  the  cases  of 
leukemia,  heart  and  amyloid  disease,  in  which  the  patients 
certainly  did  not  die  from  the  effects  of  the  excision,  but 
from  the  original  incurable  disease,  there  remain  fifty-six  cures 
in  eighty-five  cases,  i.  e.,  65.9  per  cent.,  or  two-thirds  of  all  the 
cases. 


^  O.  Vulpius,  Beibr.  z.  klin.  Chir.,  vol.  xi.  p.  655  ; 
2  Only  one  was  permanent. 


1894. 


THE    SPLEEN  235 

Since  therefore  we  learn  from  innumerable  experiments  on 
man  and  animals  that  the  absence  of  the  splenic  functions  does 
not  endanger  the  life  and  health  of  the  individual,  the  sug- 
gestion occurs  that  the  functions  of  this  organ  may  have  some 
connection  with  the  sexual  functions.  So  far  as  we  are  aware, 
all  the  functions  of  our  body  serve  directly  or  indirectly  two 
purposes  only :  the  preservation  of  the  individual  and  the 
maintenance  of  the  race.  It  would  be  interesting  to  know 
whether  the  persons  whose  spleen  has  been  removed  show  any 
alteration  in  their  sexual  life.  As  regards  animals,  the  follow- 
ing observation  of  Miescher's^  is  in  favor  of  some  such  con- 
nection between  the  splenic  and  sexual  functions.  Miescher 
noticed  that  the  size  of  the  spleen  varied  greatly  in  the 
ßhine  salmon,  and  that  this  difference  in  its  volume  depended 
upon  the  increase  or  diminution  of  the  blood  in  it.  The 
swollen  spleen  of  a  salmon  contained  sometimes  one-fourth, 
sometimes  even  as  much  as  one-half  of  the  total  blood.  In 
the  female  this  repletion  occurs  pretty  regularly  at  certain 
definite  seasons  in  the  year :  the  spleen  is  at  its  smallest 
two  months  before  (September  and  October)  and  during 
the  period  of  spawning  (November) ;  and  swells  up  after 
this  time.  In  the  male  no  such  regularity  could  be  at- 
tested ;  although  the  spleen  was  again  at  its  smallest  in 
November  during  the  time  of  spawning.  It  appears  that  the 
spleen  regulates  the  amount  of  blood  in  the  other  organs,  as 
well  as  the  processes  of  oxidation  and  other  metabolic  phenom- 
ena, thereby  indirectly  acting  upon  the  development  of  the 
ovaries  and  testes.  A  similar  connection  between  pairing 
time  and  the  size  of  the  spleen  and  the  amount  of  blood  in 
that  organ  was  observed  by  A.  Leonard  Gaule  in  frogs." 

The  relation  of  the  splenic  to  the  sexual  functions  can- 
not however  be  of  very  great  importance,  as  may  be  inferred 
from  the  fact  mentioned  above  that  both  man  and  animals 
retain  their  powers  of  propagation  after  removal  of  the 
spleen  (compare  p.  232). 

Since  therefore  the  spleen  is  not  essential  in  the  normal 
organism  either  to  the  maintenance  of  the  individual  or  of  the 
species,  we  must  finally  inquire  whether  it  may  not  have  a 
significance  in  abnormal  conditions.  It  has  been  regarded 
as  a  means  of  protection  against  injurious  substances  and  in- 
fective germs,  which  have  entered  the  blood.  This  supposi- 
tion appeared  to  be  confirmed  by  the  fact  that  in  many 
infectious  diseases  the  spleen  swells.     This  phenomenon  seems 

^  F.  Miescher-Riisch,  Du  Bois'  Arch.,  Anat.  Abth.,  p.  193:  1881. 
^  A.  Leonard  Gaule,  Journ.  Morphol.,  vol.  viii.  p.  403  :  1893. 


236  LECTURE    XVI 

to  be  analogous  to  the  swelling  of  the  lymph-glands,  which 
evidently  has  the  object  of  retaining  and  rendering  innocuous 
the  poison  which  has  been  absorbed.  It  is  possible  that 
spleenless  animals  would  be  more  readily  infected,  and  when 
infected,  more  seriously  ill  than  normal  animals.  Observations 
on  man  are  urgently  needed  as  to  how  those  persons  whose 
spleen  has  been  removed,  withstand  the  infectious  diseases 
which  they  may  subsequently  acquire.  Such  observations,  so 
far  as  I  know,  have  never  been  carried  out,  but  the  patients 
have,  as  a  general  rule,  been  completely  lost  sight  of. 

To  the  THYMUS  has  been  ascribed  functions  similar  to  those 
of  the  spleen,  the  bone-marrow,  and  the  lymphatic  glands. 
In  its  histological  aspect  the  thymus  displays  its  close  relation 
to  the  lymphoid  organs.  Besides  leucocytes  it  contains  nucle- 
ated red  blood-corpuscles.^  We  must  therefore  assume  that 
the  red  blood-cells  are  formed  here  as  well  as  the  leucocytes. 
But  in  warm-blooded  animals  however  this  function  is  con- 
fined to  the  embryonic  period,  until  the  true  lymph-glands 
are  developed.  Later  on  it  undergoes  retrograde  changes, 
and  in  the  adult  has  almost  completely  disappeared.  That 
the  thymus  takes  no  further  part  in  extra-uterine  life  is 
apparent  from  the  experiments  of  Von  Braunschweig.^  This 
observer  remarked  that  after  bleeding  or  removal  of  the  spleen, 
the  thymus  underwent  no  change  either  in  quite  young  or  in 
full-grown  animals ;  no  increase  of  cell  division  was  observed ; 
the  number  of  karyomitoses  did  not  rise  above  the  normal. 

In  cold-blooded  animals  such  as  the  frog,  the  thymus  per- 
sists throughout  life.  In  these  instances  it  is  a  double  organ. 
In  the  frog  it  is  situated  under  the  depressor  mandibule  muscle, 
which  becomes  visible  when  the  skin  behind  the  tympanum 
and  the  angle  of  the  jaw  is  removed.  According  to  Abelous 
and  Billai'd,'  in  the  frog  excision  of  the  thymus  on  both  sides 
invariably  causes  death  three  to  fourteen  days  afterwards,  with 
the  accompaniment  of  paralytic  symptoms,  a  tendency  to  ulcera- 
tion, hydremic  consistency  of  the  blood  and  hemorrhages.  Re- 
moval of  one  thymus  however  does  not  prove  fatal  in  a  healthy 
frog ;  the  only  difference  is  that  such  an  animal  tires  more 
readily  than  a  normal  frog. 

^  J.  Schaffer,  3Iecl.  Centralhlatt,  pp.  401  and  417  :  1891 ;  and  Sitzungsber.  der 
Wiener  Akad.  d.  Wissensch.  Math-natur.  Kl.,  vol.  cii.  p.  336  :  1894. 

2  R.  von  Braunschweig,  "  Exper.  Unters,  üb.  d.  Verhalten  der  Thymus  bei 
der  Regeneration  der  Blutkörperchen,"  Diss.  Dorpat :  1891. 

3  Abelous  et  Billard,  Arch.  d.  Physiol.,  5  (viii.),  p.  898  :  1896. 


LECTURE   XVII 


GASES     OF     THE     BLOOD     AND     RESPIRATION BEHAVIOR     OF 

OXYGEN     IN     THE     PROCESSES     OF     EXTERNAL 
AND     INTERNAL    RESPIRATION 

In  our  remarks  on  the  composition  of  blood,  no  account 
has  been  given  of  its  gaseous  constituents.  Three  gases  can 
be  pumped  out  of  blood  :  ^  oxygen,  carbonic  acid,  and  nitro- 
gen. 

The  amount  of  nitrogen  is  inconsiderable ;  it  does  not  occur 
here  in  larger  quantities  than  it  does  in  watery  fluids  which 
come  into  contact  with  atmospheric  air.  Nitrogen  is  simply 
absorbed  by  the  blood,^  and  it  appears  to  take  no  part  in  vital 
processes.^ 

The  two  other  gases,  on  the  other  hand,  are  of  great  physio- 
logical importance :  oxygen  is,  as  we  have  seen,  an  essential 
food-stuif,  the  most  potent  source  of  energy ;  carbonic  acid  is 
one  of  the  end-products  of  metabolism,  the  compound  in  which 
the  bulk  of  the  carbon  leaves  the  animal  body. 

'  A  diagram  and  descrii)tion  of  the  apparatus  used  for  pumping  out  the  gases 
— the  gas-pump  of  Ludwig  and  of  Pflüger — are  given  in  every  text-book  of  gen- 
eral physiology.  As  I  assume  that  all  my  readers  possess  such  a  work,  I  shall 
not  describe  it  here.  The  original  description  and  diagram  of  the  gas-pump,  with 
which  most  of  the  experiments  on  the  blood-gases  were  carried  out  in  Ludwig's 
laboratory,  will  be  found  in  Alexander  Schmidt's  paijer  in  Berichte  über  die 
Verhandl.  d.  k.  sächsischen  Ges.  d.  Wissensch.  sii  Leipzig,  Math,  physik.  Classe, 
vol.  xix.  p.  30 :  1867  ;  and  the  description  of  the  apparatus  constructed  by 
Geissler  and  Pflüger  in  Pflüger's  "  Untersuchungen  aus  dem  physiologischen 
Laboratorium  zu  Bonn,"  p.  183  :  Berlin,  1865.  For  the  methods  of  gas-analysis, 
vide  Bunsen,  "  Gasometrische  Methoden,"  Braunschweig,  2d  edit.:  1877;  and 
J.  Geppert,  "  Die  Gasanalyse  und  ihre  physiologische  AuAvendung  nach  verbes- 
serten Methoden":  Berlin,  1866. 

2  A  knowledge  of  the  laws  that  govern  the  absorption  of  gases  is  essential  for 
the  comprehension  of  the  respiratory  processes.  The  beginner  who  is  not  thor- 
oughly conversant  with  Dalton's  law,  the  meaning  of  coefficient  of  absorption, 
partial  pressure,  &c.,  must  study  a  text-book  of  physics  before  proceeding  with 
this  and  the  following  lectures. 

^  The  theory  that  a  small  part  of  the  nitrogen  issues  as  a  free  element  from 
the  decomposition  and  oxidation  of  the  nitrogenous  food-stuffs  in  the  animal  body, 
has  been  upheld  by  some  until  quite  recently,  but  has  never  been  confirmed  by 
accurate  experiment.  For  this  tedious  contest,  vide  Pettenkofer  and  Voit, 
Zeitschr.  f.  Biolog.,  vol.  xvi.  p.  508  :  1880 ;  Seegen  and  Norwak,  Pflüger's  Arch., 
vol.  XXV.  p.  383 :  1881 ;  Hans  Leo,  Pflüger's  Arch.,  vol.  xxvi.  p.  218  :  1881 ;  J. 
Eeiset,  Compt.  rend.,  vol.  xcvi.  p.  549  :  1883.  The  earlier  literature  is  quoted  in 
these  works. 

237 


238  LECTTJEE    XVII 

The  absorption  of  oxygen  and  the  excretion  of  carbonic 
acid  take  place  among  the  lower  animals  over  the  whole  surface 
of  the  body ;  among  the  higher  animals,  j^rincipally  or  ex- 
clusively in  differentiated  organs,  such  as  lungs,  gills,  and 
tracheae.  This  process  is  termed  external,  as  distinguished 
from  internal,  respiration,  which  last  term  we  apply  to  the 
consumption  of  oxygen  and  the  formation  of  carbonic  acid  in 
the  tissues.  A  few  authors  understand  by  this  latter  term,  how- 
ever, only  the  physical  process  of  the  interchange  of  gases 
through  the  walls  of  the  blood-capillaries  (the  diffusion  of  car- 
bonic acid  from  the  tissues  into  the  blood,  and  of  oxygen  from 
the  blood  into  the  tissues),  and  not  the  chemical  processes  of 
oxidation,  of  the  assimilation  of  oxygen  and  the  formation  of 
carbonic  acid  in  the  tissue  cells.  Venous  blood  is  rendered 
arterial  by  the  process  of  external  respiration ;  arterial  blood 
venous  by  that  of  internal  respiration. 

As  the  skin  and  the  lungs  are  also  tissues  requiring  oxygen 
for  the  performance  of  their  functions,  the  process  of  internal 
respiration  goes  on  at  the  same  time  along  with  that  of  external 
respiration — the  latter  preponderating  in  the  lung.  For  this 
reason  the  pulmonary  vein  carries  arterial  blood  to  the  heart. 
The  former  process  preponderates  in  the  skin  of  most  animals, 
and  the  blood  contained  in  the  cutaneous  veins  is  therefore 
venous. 

We  will  now  consider  more  closely  the  behavior  of  the 
oxygen  and  carbonic  acid  in  the  processes  of  external  and  in- 
ternal respiration.     Let  us  first  take  oxygen. 

Arterial  dog's  blood,  which  has  served  for  most  of  the 
analyses  on  the  gases  of  blood,^  contains  in  100  vols,  from  19 
to  25  vols,  of  oxygen,  computed  at  0°  C,  and  760  mm.  Hg. 
The  amount  of  oxygen  in  the  arterial  blood  of  herbivora  (sheep, 
rabbit)  is  found  to  be  smaller,  viz.,  from  10  to  15  volumes 
per  cent.^ 

This  amount  of  oxygen  is  far  too  large  to  remain  merely 
absorbed  in  the  blood.  One  hundred  volumes  of  water  absorb 
4  vols,  of  oxygen  at  0°  C.  from  an  atmosphere  of  pure  oxygen  ; 
and  from  the  ordinary  atmosphere,  in  which  the  tension  of  the 
oxygen  is  five  times  less,  it  would  therefore  absorb  less  than 
1  vol.  of  oxygen,  and  at  the  temperature  of  the  body  even  still 
less.  Watery  solutions  also  absorb  less  than  pure  water ; 
a  large  proportion  of  the  10  to  25  vols,  of  oxygen  in  arterial 

^  Pflüger,  Centralhl.  f.  d.  med.  Wissensch.,  p.  722  :  1867  ;  and  Pfliiger's  Arch., 
vol.  i.  p.  288:  1868.    The  previous  analyses  are  also  given  here. 

2  Sczelkow,  Du  Bois'  Arch.,  p.  516:  1864;  Preyer,  Wiener  med.  Jahrher., 
p.  145  :  1865 ;  Fr.  Walter,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol,  vii.  p.  148  :  1877. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  239 

blood  must  therefore  be  chemically  combined.^  We  know, 
in  fact,  that 'it  is  the  hemoglobin  which  serves  for  this  loose 
combination.^  This  is  shown  by  the  fact  that  a  pure  solution 
of  hemoglobin,  containing  the  same  amount  of  hemoglobin 
as  the  blood,  combines  with  as  much  oxygen  and  gives  off 
as  much  in  vacuo  as  the  blood  does.  The  larger  proportion 
of  oxygen  in  dog's  blood  than  in  the  blood  of  herbivora 
is  explained  by  the  fact  that  the  former  is  endowed  with 
a  larger  amount  of  blood-corpuscles  and  of  hemoglobin.  The 
amount  of  hemoglobin,  and  therefore  of  oxygen,  is  much  less 
considerable  in  the  blood  of  cold-blooded  than  in  that  of  warm- 
blooded animals. 

The  compound  of  oxygen  with  hemoglobin,  or  '  oxyhemo- 
globm,'  is  well  known  to  be  of  a  lighter  color  than  reduced 
hemoglobin,  and  shows  different  lines  of  absorption  in  the 
spectrum.  The  bright  red  coloring  of  arterial,  and  the  dark 
red  tint  of  venous,  blood  depend  upon  this  fact. 

If  oxygen  is  chemically  combined  with  hemoglobin,  we 
should  expect  them  to  be  combined  in  molecular  proportions. 
It  would  be  interesting  to  ascertain  how  many  atoms  of  oxygen 
go  to  one  atom  of  iron.  The  analyses  made  up  to  the  present 
time  are  not  exact  enough  for  this  purpose ;  they  show  how- 
ever that  about  2  or  3  atoms  of  oxygen  correspond  to  1  atom 
of  iron.-^  The  figures,  so  far,  only  demonstrate  that  there  is  at 
least  four  times  as  much  oxygen  taken  up  in  the  transition  of 
hemoglobin  into  oxyhemoglobin,  as  there  is  in  the  transition 
from  suboxid  to  oxid  of  iron,  or  from  ferrocyanid  to  ferricy- 
anid  of  potassium.  Possibly  the  sulphur  of  the  hemoglobin 
also  plays  a  part  in  the  loose  oxygen  compound,  and  a  similar 
part  may  be  assigned  to  the  sulphur  atoms  in  all  proteids. 
It  is  noteworthy  that,  according  to  previous  analyses,  the 
animals  that  require  more  oxygen  (compare  Lecture  XIII.) 
have  likewise  more  sulphur  in  their  hemoglobin.  Four  atoms 
of  sulphur  in  the  hemoglobin  of  the  horse,  six  in  that  of  the 
dog,  and  nine  in  that  of  the  hen,  go  to  two  atoms  of  iron.*  Is 
this  an  accidental  correspondence? 

^Liebig  iu  his  Ann.  d.  Chem.  u.  Pharm.,  vol.  Ixxix.  p.  112:  1851;  Lothar 
Meyer,  "Die  Gase  des  Blutes,"  Dissert.:  Göttingen,  1857;  also  Henle  and 
Pfeufer's  Zeitschr.  f.  rat.  Med.,  N.  F.,  vol.  xviii.  p.  256  :  1857. 

2 Hoppe-Seyler,  Arch.  f.  path.  Anat.,  vol.  xxix.  p.  598:  1864;  and  Med. 
chem.  Unters.,  p.  191 :  1867. 

^  Hiifner,  Zeitschr.  f.  physiol.  Chem.,  vol.  i.  pp.  317,  386  :  1877 ;  vol.  iii.  p.  1 : 
1880.  John  Marshall,  Zeitschr.  /.  physiol.  Chem.,  vol.  vii.  p.  81 :  1883.  Hiifner, 
Zeitschr.  f.  physiol.  Chem.,  vol.  viii.  p.  358:  1884.  The  previous  determinations 
are  quoted  here.  Compare  also  Hoppe-Seyler,  ibid.,  vol.  xiii.  p.  477  :  1889.  G. 
Hiifner,  Du  Bois'  Arch.,  p.  130 :  1894.  ■ 

*A.  Jaquet,  "  Beitr.  zur  Kenntniss  des  Blutfarbstoffes,"  Dissert.:  Basel, 
1889. 


240  LECTURE    XVII 

The  oxygen  in  loose  combination  with  the  hemoglobin  may- 
be displaced  by  an  equal  volume  of  carbonic  oxid/  or  of  nitric 
oxid/  a  fact  which  likewise  speaks  for  the  chemical  union  of 
the  oxygen. 

It  may  be  objected  that  the  oxyhemoglobin  combination 
could  hardly  be  destroyed  by  a  mere  vacuum,  if  it  were  really 
a  chemical  compound.  But,  as  a  matter  of  fact,  it  is  not 
the  vacuum  which  splits  up  the  oxyhemoglobin,  but  the  heat. 
A  solution  of  oxyhemoglobin  may  be  evaporated  to  dryness 
at  a  very  low  temperature,  i.  e.,  below  0°  C.  in  vacuo;  the 
oxyhemoglobin  crystals  are  not  affected.  The  higher  the  tem- 
perature, the  greater  must  be  the  pressure  of  oxygen  in  order 
to  counterbalance  the  dissociating  force  of  heat.  The  affinity 
of  a  substance  increases  in  proportion  to  the  number  of  atoms 
which  cooperate  in  the  attraction,  or  in  proportion  to  the 
number  of  atoms  in  the  unit  of  volume.  This  phenomenon 
is  called  the  influence  of  mass.^  Two  antagonistic  forces 
are  at  work  in  the  formation  and  decomposition  of  oxyhemo- 
globin :  heat  endeavors  to  separate,  chemical  affinity  seeks  to 
unite.  Affinity  increases  with  the  influence  of  mass,  with  the 
density,  with  the  partial  pressure  of  the  oxygen.  The  vacuum 
therefore  acts  only  by  reducing  the  mass-influence  of  the  oxy- 
gen to  a  minimum,  and  thus  enabling  the  antagonistic  heat  to 
attain  supremacy. 

1  may  here  remind  my  readers  of  an  analogous  phenomenon 
well  known  in  inorganic  chemistry.  When  chalk  is  burnt,  the 
carbonic  acid  is  separated  from  the  lime  by  heat.  But  this 
separation  does  not  take  place  in  an  atmosphere  of  pure 
carbonic  acid ;  on  the  contrary,  quicklime  unites  with  COg  at  a 
high  temperature,  if  the  partial  pressure  of  the  carbonic  acid 
be  sufficient.  If  the  carbonate  of  lime  is  to  be  rapidly  converted 
into  quicklime,  a  stream  of  another  gas  must  be  passed  over  it, 
so  as  to  reduce  the  partial  pressure  of  the  carbonic  acid.  The 
same  thing  takes  place  in  the  relation  of  hemoglobin  to  oxygen. 

^  Cl.  Bernard,  "  Lejons  sur  les  effets  des  substances  toxiques,"  &c. :  Paris, 
1857  ;  Hoppe-Seyler,  Virchow's  Arch.,  vol.  xi.  p.  288 :  1857  ;  and  vol.  xxix.  pp. 
233,597:  1863;  Lothar  Meyer,  "De  Sanguine  oxydocarbonico  infecto,"  Dissert. 
Vratislavise  :  1858;  Hoppe-Seyler,  Med.  chem.  Unters.,  p.  201 :  1867;  Zeitschr.  f. 
physiol.  Chem.,  vol.  1,  p.  131:  1877;  John  Marshall,  Zeitschr.  f.  physiol.  Chem., 
vol.  vii.  p.  81:  1883;  R.  Kiilz,  ibid.,  p.  384;  G.  Hiifner,  Journ.  f.prakt.  Chem., 
N.  F.,  vol.  xxx.  p.  67  :  1884. 

2  L.  Hermann,  Du  Bois'  Arch.,  p.  469  :  1865 ;  Hoppe-Seyler,  Med.  chem. 
Unters.,  p.  204:  18G7 ;  W.  Preyer,  "Die  Blutkrystalle,"  p.  144:  Jena,  1871; 
Podolinski,  Pfliiger's  Arch.,  vol.  vi.  p.  553  :  1872. 

^  For  the  explanation  of"  the  phenomenon  of  the  influence  of  mass,  afforded 
by  the  mechanical  theory  of  heat,  see  Lothar  Meyer,  "Die  modernen  Theorien 
der  Chemie,"  5th  edit.,  p.  479:  Breslau,  1884,  or  "Lehrbuch  der  allgemeinen 
Chemie,"  by  W.  Ostwald,  vol.  ii.  part  ii. :  Leipzig,  1887. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  241 

In  the  alveoli  of  the  lungs,  where  the  partial  pressure  of  the 
oxygen  is  considerable,  the  hemoglobin  is  completely  or  very 
nearly  saturated  with  oxygen.  In  the  capillaries  of  the  tissues, 
where  the  oxygen  that  has  been  simply  absorbed  diffuses  itself 
or  enters  into  combination  with  reducing  substances,  so  that 
the  partial  pressure  diminishes,  a  portion  of  the  combined 
oxygen  is  at  once  set  free  by  the  liberating  force  of  heat,  and 
the  partial  pressure  of  the  oxygen  rises  again  till  it  balances 
the  effect  of  the  heat.  In  this  way,  the  red  blood-corpuscle  is 
always  surrounded  by  oxygen  under  a  definite  pressure. 

This  arrangement  serves  a  double  purpose.  Firstly,  there 
is  far  more  oxygen  brought  to  each  tissue  by  the  blood-current 
in  a  definite  period  than  would  be  possible  by  simple  absorption 
of  the  oxygen  without  chemical  combination.  The  processes 
of  oxidation  might  go  on  much  more  rapidly,  and  yet  there 
would  not  be  a  scarcity  of  oxygen.  The  amount  of  oxygen 
in  the  plasma  is  very  little  less  when  the  oxygen  is  lavishly 
used  up  than  when  it  is  economically  expended.  The  store 
of  oxygen  in  the  capillaries  is  never  exhausted  under  normal 
conditions.  In  venous  blood,  at  least  5  per  cent,  by  vol- 
ume of  oxygen  is  always  found,  and  generally  far  more. 
Only  in  asphyxial  blood  does  the  oxygen  almost  entirely  dis- 
appear.^ 

Secondly,  the  chemical  combination  of  oxygen  offers  the 
great  advantage  that  the  intensity  of  the  processes  of  oxidation 
is,  to  a  great  extent,  independent  of  the  partial  pressure  of  the 
oxygen  in  the  surrounding  media.  Direct  experiment  has 
shown  that  the  partial  pressure  of  the  oxygen  in  the  surround- 
ing atmosphere  may  increase  threefold  or  diminish  to  one-half 
without  any  disturbance  being  manifested  in  the  breathing  of  a 
mammal.^ 

When  the  partial  pressure  is  reduced  still  further,  the  fre- 
quency of  respiration  increases ;  and  when  it  sinks  to  3.5  per 
cent,  of  an  atmosphere,  the  animals  die.^ 

Fraenkel  and  Geppert*  allowed  dogs  to  breathe  rarefied 
atmospheric  air,  and  analyzed  the  gases  of  their  arterial  blood. 

^  N.  Stroganow,  Pfliiger's  Arch.,  vol.  xii.  j).  22  :  1876.  The  previous  experi- 
ments on  the  blood  of  asphyxiated  animals  are  quoted  here. 

^"VVilh.  Müller,  Ann.  d.  Chem.  u.  Fharm.,  yoI.  cviii.  p.  257:  1858.  Paul 
Bert,  "La  pression  barometrique  ":  Paris,  1878.  A.  Fraenkel  and  J.  Geppert, 
"  Ueber  die  Wirkungen  der  verdünnten  Luft  auf  den  Organismus":  Berlin, 
Hirschwald,  1883.  Vide  also  L.  de  Saint  Martin,  Comiot.  rend.,  vol.  xcviii.  p. 
241 :  1884 ;  and  S.  Lukjanow,  Zeitschr.  f.  physiol.   Chem.,  vol.  viii.  p.  313  :  1884. 

^N.  Stroganow,  Pflüger's  Arch.;  vol.  xii.  p.  31 :  1876.  Au  account  of  former 
work  is  given  here. 

*  Fraenkel  and  Geppert,  loc.  cit.,  p.  47.  The  experiments  similar  to  those  of 
Paul  Bert  are  also  critically  discussed  here. 

16 


242  LECTURE    XVII 

They  found  that  when  the  pressure  of  air  sank  to  410  mm.  Hg. 
the  normal  amount  of  oxygen  was  retained  in  the  arterial 
blood.  If  the  pressure  of  air  sank  to  between  378  and  365 
mm.  Hg.,  or  to  half  an  atmosphere,  the  amount  of  oxygen  in 
the  arterial  blood  was  somewhat  diminished.  But  it  was  not 
until  the  atmospheric  pressure  sank  below  300  mm.  that  a  con- 
siderable decrease  of  oxygen  was  observed. 

The  partial  pressure  of  oxygen  might  a  priori  have  been 
thought  to  exercise  a  much  slighter  influence  than  we  have 
shown  it  to  possess ;  for,  according  to  the  experiments  of 
Worm  Müller/  the  blood  outside  the  body  becomes  almost  com- 
pletely saturated  with  oxygen  on  being  shaken  with  atmospheric 
air  of  only  75  mm.  Hg.  But  these  experiments  were  carried 
out  at  the  temperature  of  the  room.  At  the  temperature  of  the 
body,  decomposition  of  the  oxyhemoglobin  begins  at  a  higher 
partial  pressure,  as  Paul  Bert  ^  and  Fraeukel  and  Geppert  ^  have 
shown.  And  besides  it  must  be  remembered  that,  in  the  lungs, 
oxygen  at  a  low  tension  cannot  be  diffused  through  the  walls 
of  the  alveoli  rapidly  enough  to  saturate  each  blood-corpuscle 
during  its  short  transit  through  the  capillaries. 

The  experience  obtained  in  mountain  and  balloon  ascents  is 
in  complete  harmony  with  the  results  of  the  experiments  on 
animals.^  Real  dyspnea  does  not  begin  till  a  height  of  5000 
meters  is  reached,  which  corresponds  to  a  mercurial  pressure  of 
400  mms.  Human  beings  and  animals  live  as  well  on  the  high 
plateaus  of  the  Andes  at  4000  meters  above  the  level  of  the  sea 
as  on  the  sea-coast. 

The  poisonous  influence  of  carbonic  oxid  depends  perhaps 
only  on  the  displacement  of  the  oxygen.  J.  Haldane^  found 
that  the  poisonous  effect  was  smaller,  the  greater  the  partial 
pressure  of  the  oxygen.  If  the  oxygen  pressure  amounted  to 
two  atmospheres,  the  carbonic  oxid  pressure  could  be  raised  to 
as  much  as  one  atmosphere,  without  any  inconvenience  to  the 
animal.  Animals  devoid  of  hemoglobin  (e.  g.,  black-beetles), 
are  not  influenced  in  the  slightest  degree  by  the  presence  of 
carbonic  oxid  in  the  air. 

We  must  now  ask  in  what  organs  and  tissues  of  our  bodies 
the  oxygen  gets  used  up. 

Lavoisier,  who  first  recognized  the  importance  of  oxygen  in 
vital  processes,  thought  that  combustion  occurred  exclusively 

*  Worm  Müller,  Bcr.  d.  sacks.  Ges.,  vol.  xxii.  p.  351 :  1870. 
2  Paul  Bert,  "  La  pression  barometrique,"  p.  691. 

'  Fraenkel  and  Geppert,  "  Ueber  die  Wirkungen  der  verdünnten  Luft  auf 
den  Organismus,"  p.  57. 

*  Paul  Bert,  loc.  eit.,  gives  an  interesting  account  of  these  experiences. 
^  J.  Haldane,  Journ.  of  Physiol.,  vol.  xviii.  p.  201 :  1895. 


GASES    OF    THE    BLOOD    AXD    RESPIRATION  243 

in  the  lung.  It  was  not  until  Magnus  ^  had  analyzed  the  gases 
of  the  blooJ  that  it  was  proved  that  oxygen  passes  on  to  the 
capillaries,  and  there  partially  disappears.  But  the  question  as 
to  whether  the  processes  of  oxidation  are  completed  only  within 
the  closed  blood-current,  or  whether  free  oxygen  is  diffused 
through  the  walls  of  the  capillaries  into  the  tissues,  has  not  yet 
been  decided. 

The  former  theory,  i.  e.,  that  the  oxygen  is  consumed  within 
the  blood-vessels,  has  found  supporters  even  up  to  the  present 
time.  The  most  obvious  objection  to  it  is  that  kinetic  energy 
is  liberated  in  the  tissues,  and  particularly  in  the  muscles,  and 
that  the  most  fertile  source  of  energy  lies  in  the  affinity  of 
oxygen  for  the  substances  of  nutrition.  But,  on  the  other  hand, 
we  know  that  there  is  stored  up  in  food  a  considerable  amount 
of  chemical  potential  energy,  which  is  converted  into  kinetic 
energy  by  the  mere  decomposition  of  the  food-stuffs,  without 
any  oxidation  taking  place  (compare  Lectures  X.  and  XXIII.). 
The  amount  of  this  potential  energy  is  not  exactly  known  ;  it 
must  be  admitted  that  it  may  be  sufficient  to  perform  the  work 
of  muscle,  and  that  the  products  of  decomposition  thus  formed 
may  diffuse  into  the  capillaries,  to  be  there  oxidized,  and  then 
to  serve  as  sources  of  bodily  heat. 

This  view  appeared  to  receive  confirmation  from  the  follow- 
ing experiment  of  Ludwig  and  Alexander  Schmidt.^  It  has 
already  been  mentioned  that  the  blood  of  animals  which  have 
died  from  suffocation  contains  only  traces  of  oxygen,  and  some- 
times none  at  all.  If  oxygen  be  added  to  such  blood  outside 
the  body,  a  part  of  the  oxygen  thus  artificially  introduced 
rapidly  disappears,  and  the  carbonic  acid  is  increased.  The 
blood  from  asphyxiated  animals  contains  substances  that  are 
readily  oxidized.  The  blood  of  other  animals  also  combines  with 
some  oxygen  outside  the  body,^  but  the  oxygen  absorbed  is  much 
less  in  amount  and  disappears  much  more  slowly  than  in  the  case 
of  the  blood  from  asphyxiated  animals.*  Ludwig  and  Alexander 
Schmidt  explain  these  facts  thus :  Under  normal  conditions, 
readily  oxidized  compounds  are  continually  finding  their  way 
from  the  tissues  into  the  capillaries,  where  they  are  immedi- 
ately decomposed  by  the  free  oxygen,  so  that  they  cannot  be 
traced  in  normal  blood.     In  asphyxiated  animals,  on  the  other 

^  G.  Magnus,  Ann.  d.  Physik,  vol.  xl.  p.  583  :  1837 ;  and  vol.  Ixiv.  p.  177  : 
1845. 

^  Alex.  Schmidt,  Ber.  über  die  Verhandl.  der  sacks.  Gcs.  der  Wissensch.  zu 
Leipzig,  Math.  phys.  Classe,  vol.  xix.  p.  99 :  1867.  Vide  also  N.  Stroganow, 
Pfliiger's  Arch.,  vol.  xii.  p.  41 :  1876. 

3  Pflüger,  Centralbl.f.  d.  raed.  Wissensch.,  pp.  321,  722:  1867. 

4  Alex.  Schmidt,  loc.  cit.,  p.  108. 


244  LECTURE    XVII 

hand,  tlney  remain  stored  up  in  the  blood  in  consequence  of  the 
absence  of  oxygen.  According  to  the  laws  which  govern  the 
diffusion  of  gases,  we  should  expect  to  find  that  the  oxygen  in 
the  blood  would  penetrate  the  liquids  of  all  the  tissues.  It  is 
however  conceivable  that  the  oxygen  may  be  hindered  from 
doing  so  by  the  reducing  substances  which,  flowing  unintermit- 
tently  from  the  tissues  into  the  blood,  meet  the  oxygen  on  its 
way  and  prevent  its  advance  beyond  the  capillary  wall. 

The  opposite  view,  that  oxidation  takes  place  in  the  other 
tissues  as  well,^  rests  upon  the  following  facts  of  comparative 
physiology.^  It  is  well  known  that  nearly  all  the  lower  animals 
which  have  no  blood,  die  at  once  without  oxygen,  and  that  this 
source  of  energy  is  indispensable  to  every  cell.^  The  vegetable 
cell  has  likewise  essentially  the  same  metabolism,  and  cannot 
live  without  free  oxygen.  The  higher  animals,  with  a  diiferen- 
tiated  system  of  blood-vessels,  require  oxygen  in  the  first  stages 
of  existence,  even  before  the  formation  of  blood-corpuscles,  as 
the  respiration  of  a  bird's  egg  shows.* 

Nevertheless  we  cannot  admit  that  these  facts  afford  in- 
dubitable proof  of  respiration  in  the  tissues  of  the  higher 
animals  when  fully  developed ;  for  the  essence  of  the  higher 
organization  consists  in  the  fact  that  there  is,  synchronous  with 
the  differentiation  of  the  tissues  and  organs,  a  division  of 
labor.  It  is  quite  conceivable  that  decomposition  and  oxida- 
tion may  take  place  in  the  same  cell  among  the  lower  animals 
only,  and  that  in  the  more  highly  organized  ones  the  duty  of 
oxidation  is  exclusively  relegated  to  the  blood,  the  processes  of 
decomposition  going  on  in  the  other  tissues. 

But  it  can  be  shown  that  oxidation  also  occurs  in  the 
tissues  of  insects,  which  possess  a  vascular  system  although 
not  so  highly  developed  as  the  vertebrata.  This  is  proved  by 
the  fact  that  the  finest  branches  of  a  trachea  run  down  as  far 
as  the  individual  cells  of  the  tissue.^     The  observations  made 

^  The  first  decided  advocate  of  this  view  was,  so  far  as  I  know,  Moritz 
Traube,  Virchow's  Arch.,  vol.  xxi.p.  386  :  1861. 

2  Pflüger,  in  his  Arch.,  vol.  x.  p.  270  :  1875. 

^  It  is  still  a  matter  of  controversy  whether  certain  organisms  of  the  lowest 
kind — yeast-cells,  certain  bacteria — can  live  entirely  without  free  oxygen,  "  anae- 
robic." It  appears  however  that  this  question  may  now  be  answered  in  the 
affirmative.  VideJ.  W.  Gunning,  Journ.f.prakt.  Chem.,  vol.  xvi.  p.  314  :  1877  ; 
vol.  xvii.  p.  266  :  1878;  and  vol.  xx.  p.  434:  1879;  Nencki,  Jour^i.  f.  x>rakt. 
Chem.,  vol.  xix.  p.  337  :  1879  ;  Br.  Lachowicz  und  Nencki,  Pfliiger's  Arch.,  vol. 
xxxiii.  p.  1 :  1883  ;  and  Nencki,  Pfliiger's  Arch.,  vol.  xxxiii.  p.  10  :  1883.  Com- 
pare also  G.  Bunge,  "lieber  das  Sauerstoffbedürfniss  der  Darmparasiten," 
Zeitschr.  f.  physiol.  Chem.,  vol.  viii.  p.  48  :  1883. 

*  J.  JBaumgärtner,  "  Der  Athmungsprocess  im  Ei,"  Freiburg  i.  B.  :  1861. 

5  Kupflfer,  "Beiträge  zur  Anatomie  und  Physiologie,  als  Festgabe  C.  Lud- 
wig gewidmet  von  seinen  Schülern,"  p.  67  :  1875  ;  Fiukler,  Pflüger's  Arch.,  vol. 
X.  p.  273  :  i875. 


GASES    OF    THE    BLOOD    AND    EESPIHATION  245 

by  Max  Schultze  ^  on  the  Lampyris  splendidula  are  particularly 
conclusive,  .  In  the  glow  organs  of  this  animal  certain  cells 
adhere  to  the  tracheal  endings,  "  like  the  flowerets  of  an  um- 
belliferous plant."  These  cells,  as  well  as  the  tracheal  endings, 
stain  a  deep  black  with  osmic  acid,  owing  to  the  separation  of 
the  metallic  osmium ;  consequently  there  is  present  in  these 
cells  a  substance  with  a  powerful  attraction  for  oxygen.  It 
may  therefore  readily  be  supposed  that  this  substance,  by  com- 
bining with  the  oxygen  introduced  through  the  tracheae,  brings 
about  the  development  of  light.  The  illuminating  power  of  the 
paired  glow  organs  continues  after  they  have  been  isolated,  and 
even  after  a  microscopic  section  has  been  made.  Max  Schultze 
observed  under  the  microscope  that  "  with  the  rhythmic  increase 
and  diminution  of  the  light,  which  these  animals  generally  ex- 
hibit distinctly,  the  first  appearance  of  the  light  is  characterized 
by  minute  coruscations  in  the  glow  organ,  which  correspond  in 
number  and  arrangement  to  the  terminal  cells  of  the  tracheae." 
When  the  oxygen  is  withdrawn,  the  illuminating  power  ceases.^ 
Max  Schultze  also  remarks  that  the  tracheal  terminations  in 
other  organs,  as  well  as  those  in  the  glow  organs,  are  rapidly 
stained  black  if  the  animals  be  placed  alive  in  osmic  acid. 

In  view  of  these  facts,  it  cannot  be  doubted  that  free 
oxygen  is  used  up  in  the  tissues  of  insects.  A  critical  observer 
will  nevertheless  hesitate  before  applying  these  results  to  the 
vertebrata.  In  the  case  of  the  latter,  it  is  only  in  the  placenta 
of  mammals  and  in  the  salivary  glands  that  the  oxygen  has 
been  definitely  proved  to  make  its  way  out  through  the  capillary 
walls. 

The  blood  of  the  umbilical  vein  is  of  a  brighter  red  than 
that  of  the  umbilical  arteries,  and  oxyhemoglobin  can  be 
traced  in  the  former  by  the  spectroscope.^  It  is  well  known 
that  the  blood-vessels  of  the  mother  and  of  the  embryo  do  not 
communicate  in  the  placenta ;  they  form  two  separate  capillary 
systems.  The  oxygen  must  therefore  be  first  diffused  through 
the  capillary  walls  of  the  mother's  vascular  system,  and  then 
through  those  of  the  fetus,  before  reaching  the  blood  of  the 
latter. 

^  Max  Schultze,  Arch.  f.  mik.  Anat.,  vol.  i.  p.  124:  1865. 

2  An  interesting  account  of  the  numerous  observations  on  the  illuminating 
power  of  various  animals,  and  its  dependence  on  the  presence  of  oxygen,  is 
given  by  Milne  Ed\yards,  "  Lecons  sur  la  physiologie  et  I'anatomie  comparee," 
vol.  viii.  pp.  93-120:  Paris,  1863;  and  by  Pflüger,  in  his  Arch.  f.  d.  ges.  Phys., 
vol.  X.  pp.  275-300 :  1875.  For  the  experiments  on  the  chemical  side,  vide 
Radziszewski,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  xvi.  p.  597  :  1883,  where  the  pre- 
vious writings  on  this  siibject  are  quoted. 

3  Zweifel,  Arch.  f.  Gynäkologie,  vol.  ix.  p.  291 :  1876  ;  Zuntz,  Pflüger's  Arch., 
vol.  xiv.  p.  605 :  1877. 


246  LECTURE    XVII 

That  oxygen  passes  through  the  capillary  wall  in  the 
salivary  glands  is  apparent,  for  the  simple  reason  that  the 
saliva  contains  free  oxygen.  So  large  an  amount  of  oxygen 
passes  out  of  the  blood  therefore,  that  the  cells  of  the 
glandular  tissue  cannot  consume  it,  and  the  excess  escapes 
with  the  secretion.  Pflüger  ^  ascertained  the  presence  of 
absorbed  oxygen  in  the  submaxillary  secretion  with  the  aid 
of  the  gas-pump  ;  he  found  that  it  amounted  to  from  0.4  to  0.6 
per  cent,  of  the  volume  of  the  saliva.  This  fact  was  confirmed 
by  Hoppe-Seyler,  who  used  a  very  sensitive  test  for  free  oxygen, 
a  hemoglobin  solution  which,  on  coming  into  contact  with 
fluids  containing  oxygen,  at  once  shows  the  absorption-bands 
characteristic  of  oJcyhemoglobin.^  Hoppe-Seyler  found  that 
the  secretions  of  both  the  submaxillary  and  of  the  parotid 
contained  oxygen. 

Hoppe-Seyler,  on  the  other  hand,  could  detect  no  trace  of 
oxygen  in  the  bile  and  urine  with  the  aid  of  his  sensitive 
reagent.^  Nor  has  any  free  oxygen  been  found  definitely  in 
lymph.  Free  oxygen  has  therefore  not  been  proved  with 
certainty  to  exist  in  most  organs  of  vertebrata. 

Pflüger  and  Oertmann  ^  founded  their  proof  on  the  follow- 
ing experiment.  They  showed  that  a  frog,  in  whose  vascular 
system  a  solution  of  common  salt  circulated  instead  of  blood, 
used  up  as  much  oxygen,  and  produced  as  much  carbonic 
acid  in  an  atmosphere  of  pure  oxygen,  as  a  normal  frog  would 
do.  A  fine  cannula  is  tied  into  the  central  end  of  the  abdominal 
vein^  of  a  frog,  and  a  0.75  per  cent,  solution  of  salt  injected, 
until  increasingly  diluted  blood  and  finally  pure  salt  solution 
flows  from  the  peripheral  opening  of  the  vein.^  Frogs  thus 
treated  generally  lived  one  or  two  days.  If  such  frogs  were 
introduced  into  an  atmosphere  of  pure  oxygen,  they  consumed 
as  much  oxygen  and  developed  as  much  carbonic  acid  in  from 

^  Pflüger,  in  his  Arch.,  vol.  i.  p.  686  :  1868. 

2  Hoppe-Seyler,  Zeitschr.  f.  physiol.  Chcm.,  vol.  i.  p.  135  :  1877.  The  appa- 
ratus used  by  him  to  admit  of  the  action  of  the  hemoglobin  solution  on  the 
secretion,  without  coming  in  contact  with  the  atmospheric  air,  is  described 
here. 

3  The  traces  of  oxygen  which  Pflüger  {Arch.,  vol.  ii.  p.  156 :  1869)  found  in 
the  gases  that  were  pumped  out  of  the  urine,  milk,  and  bile,  were  probably  only 
due  to  the  unavoidable  contamination  with  atmospheric  air. 

*  E.  Oertmann,  Pflüger's  Arch.,  vol.  xv.  p.  381  :  1877. 

^  The  work  of  Alex.  Ecker,  "  Die  Anatomie  des  .Frosches,"  Vieweg  and  Sohn, 
1864-1882  [translated  into  English  by  G.  Haslam,  Foreign  Biological  Memoirs  ; 
Clarendon  Press,  Oxford] ,  will  serve  to  acquaint  the  reader  with  the  anatomy  of 
the  frog.  It  is  plentifully  supplied  with  illustrations,  and  contains  a  complete 
account  of  the  literature  of  the  subject.  [A  new  edition  of  this  work,  edited  by 
Gaupp,  is  now  appearing.] 

^  This  method  of  obtaining  frogs  free  from  blood  was  first  introduced  by 
Cohnheim  (Virchow's  Arch.,  vol.  xlv.  p.  333  :  1869). 


GASES    OF    T:IE    BLOOD    AND    RESPIRATION  247 

ten  to  twenty  hours  as  a  normal  animal.  Oertmann  concluded 
from  this  experiment  that  oxidation  proceeded  only  in  the 
tissues,  because  they  alone  used  up  as  much  oxygen  as  the 
tissues  and  the  blood  together.  But  this  is  not  a  necessary 
conclusion.  The  facts  may  equally  well  be  interpreted  in 
support  of  the  opposite  view.  It  might  be  argued  in  this 
case  that,  again,  only  processes  of  decomposition  had  taken 
place  in  the  tissues  of  the  '  salt-frog ' ;  that  the  products  of 
decomposition  had  been  diffused  throu:gh  the  capillary  wall 
into  the  solution  of  salt  containing  oxygen,  and  had  been 
oxidized  within  the  closed  vascular  system.  The  partial  pres- 
sure of  the  oxygen,  being  five  times  greater  than  normal,  had 
made  up  for  the  want  of  hemoglobin. 

In  conclusion,  we  must  however  mention  the  following 
very  interesting  fact,  ascertained  by  Ludwig  and  his  pupils. 
Afonassiew  ^  found  that  the  reducing  substances  of  the  blood 
from  asphyxiated  animals  occur  only  in  the  blood-corpuscles, 
and  not  in  the  serum ;  and  Tschiriew  ^  found  that  the  lymph 
of  such  animals  is  also  free  from  these  substances. 

It  thus  appears  that  the  blood  is  only  concerned  in  proc- 
esses of  oxidation  in  so  far  as  living  cells  are  suspended  in 
it ;  that  all  oxidations  in  our  body  proceed  exclusively  in  the 
active  elements  of  the  tissues — in  the  cells  and  the  products  of 
the  metamorphosis,  but  not  in  the  fluids  surrounding  them. 

This  theory  is  rendered  so  probable  by  all  the  facts  and 
analogies  of  the  case  that  it  is  accepted  by  every  physiologist. 

We  have  now  to  consider  how  the  rapid  and  complete 
oxidation  of  the  food-stuflPs  in  our  tissues  is  to  be  explained. 
The  food  eaten  at  the  most  abundant  meal  becomes,  before  six 
hours  have  elapsed,  nearly  all  converted  by  oxidation  into  the 
end-products,  carbonic  acid,  water,  and  urea ;  whereas  proteid, 
fats,  and  carbohydrates  are  not  affected  by  oxygen  external  to, 
and  at  the  temperature  of,  the  body.  Other  conditions  favor- 
able to  oxidation  must  therefore  be  present  in  the  body. 

The  most  obvious  suggestion  was  that  the  alkalinity  of  the 
blood,  of  lymph,  and  of  protoplasm  had  something  to  do  with 
the  matter.  It  is  known  that  the  oxidation  of  organic  sub- 
stances proceeds  more  rapidly  in  an  alkaline  than  in  a  neutral 
or  acid  solution.  I  may  remind  my  readers  of  the  behavior 
of  pyrogallol — and,  indeed,  of  all  polyatomic  phenols — of  the 
leuco-compounds  of  numerous  dye-stuffs,  of  grape-sugar,  &c. 
The  latter,  dissolved  in  soda,  absorbs  oxygen  rapidly  at  the 
temperature  of  the  body.     But  it  must  be  remembered  that 

1  N.  Afonassiew,  Ber.  d.  sacks.  Ges.  d.  Wissensch.,  vol.  xxiv.  p.  253  :  1872. 
^  S.  Tschiriew,  ibid,,  vol.  xxvi.  p.  116  :  1874. 


248  LECTUEE   XVII 

for  this  purpose  free  alkali  is  necessary,  whereas  our  tissues 
contain  only  carbonates  or  possibly  bicarbonates  of  the  alkalies, 
since  free  carbonic  acid  penetrates  all  tissue  elements. 

Xencki  and  Sieber  ^  have  indeed  shown  that  dilute  solutions 
of  sodium  carbonate  and  grape-sugar  or  proteid  also  absorb 
oxygen.  But  the  amount  absorbed  is  small,  and  the  absorp- 
tion takes  place  very  slowly.  Schmiedeberg-  showed  that 
benzylalcohol  and  salicylaldehyde  are  not  appreciably  oxidized 
by  the  atmospheric  air  in  the  presence  of  water.  If  these 
substances  were  brought  into  contact  with  blood  or  dilute 
sodium  carbonate  solution  instead  of  water,  a  small  trace  of 
the  benzylalcohol  was  oxidized  to  benzoic  acid.  The  salicyl- 
aldehyde was  also  under  these  circumstances  imchanged.  If 
however  these  substances  were  passed  with  oxygenated  defi- 
brinated  blood  through  the  kidneys  or  lungs  of  dogs  or  pigs,  a 
considerable  amount  of  both  was  oxidized  to  benzoic  acid  and 
salicylic  acid  respectively.  The  same  result  was  obtained  when 
watery  extracts  of  these  organs  mixed  with  salicylaldehyde 
were  exposed  in  thin  layers  to  the  action  of  the  atmospheric 
oxvgeu.  The  quantity  of  salicylic  acid  formed  however  was 
only  small.  Boiling  destroyed  the  oxidizing  action  of  the 
extracts.^  It  seems  to  me  that  we  cannot  at  present  draw  any 
conclusion  as  to  the  behavior  of  the  food-stuffs  in  our  body 
from  a  consideration  of  the  changes  undergone  by  such  easily 
oxidizable  substances. 

In  order  to  explain  the  rapid  oxidation  of  fox)d-stuffs  in 
the  body,  recourse  has  been  had  to  the  assumption  that  a 
portion  of  the  inspired  oxygen  is  converted  in  our  tissues  into 
that  powerful  oxidizing  modification  termed  ozone.  Even 
Schönbein,*  the  discoverer  of  ozone,  mentioned  this  hypothesis. 
What  therefore  is  known  concerning  ozone  ? 

If  induced  currents  be  allowed  to  pass  through  oxygen, 
condensation  takes  place,  and  the  oxygen  now  contains  ozone. 
A  small  part  only  of  the  oxygen — at  most  5  per  cent. — is 
converted  into  ozone.  The  volume  of  the  ozone  amounts  to 
only  two-thirds  of  that  of  the  oxygen  from  which  it  was 
formed.  Soret^  has  ascertained  this  in  the  following  manner. 
Oil   of  turpentine  absorbs  only   the   ozone  from   oxygen  con- 

^  Nencki  and  Sieber,  Journ.  f.  prakt.  Chem.,  vol.  xxvi.  p.  1 :  1882. 

2  Schmiedeberg,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xiv.  pp.  288  and  379 : 
1881.  Compare  also Salkowski,  Zeitschr.  f.  physiol.  Chem.,  vol.  vii.  p.  155  :  1882  ; 
and  Centralhl.  f.  d.  med.  Wissensch.,  p.  849  :  1892. 

3  A.  Jaquet,  Arch.f.  exper.  Path.  u.  Pharm.,  vol.   xxix.  p.  386  :  1892. 

4  Schöllbein,  Poggendorff's  Annul.,  vol.  Ixv.  p.  171  :  1845. 

5  Soret,  Ann.  Chem.  Pharm.,  vol.  cxxvii.  p.  38  :  1863  ;  vol.  cxxx.  p.  95  :  1863  ; 
Suppl.  V.  p.  148:  1867;  Compt.  rend.,  vol.  Ivii.  p.  604:  1863. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  249 

taining  ozone,  the  amount  of  which  is  ascertained  from  the 
diminution  of  volume.  If  a  sample  of  this  oxygen  con- 
taining ozone  be  heated,  the  ozone  is  destroyed,  and  the 
volume  increases.  This  increase  of  volume  is  always  half  as 
much  as  the  diminution  of  volume  by  absorption.  Therefore 
on  heatino-  oue  volume  of  ozone  becomes  one  and  a  half  vol- 
umes  of  oxygen,  two  volumes  of  ozone  become  three  volumes 
of  oxygen.  It  follows,  both  from  this  fact  and  from  Avogadro's 
hypothesis  (that  equal  volumes  of  gas  contain  an  equal  number 
of  molecules),  that  ozone  contains  three  atoms  of  oxygen  in 
each  molecule.  Three  oxygen  molecules  of  two  atoms  each 
have  produced  two  ozone  molecules  of  three  atoms.  We  may 
imagine  that  the  two  atoms  in  the  oxygen  molecule  become 
separated  from  each  other  by  the  kinetic  energy  of  the  electric 
current,  and  each  of  them  attaches  itself  loosely  to  an  intact 
oxygen  molecule.  This  third  oxygen  atom,  thus  loosely  com- 
bined, has  a  strong  affinity  for  oxidizable  substances.^  In  fact, 
in  oxidation  by  ozone,  never  more  than  a  third  of  the  weight 
of  the  ozone  enters  into  combination,  and  no  diminution  of 
volume  of  the  oxygen  containing  ozone  occurs. 

This  theory  is  also  strictly  in  accordance  with  the  fact  that 
even  at  a  low  temperature  ozone  oxidizes  substances  which 
ordinary  oxygen  does  not  attack  except  at  a  high  temperature. 
In  the  case  of  ordinary  oxygen,  the  atoms  must  first  be  sepa- 
rated by  the  kinetic  energy  of  heat.  With  ozone,  this  was 
done  beforehand  by  the  kinetic  energy  of  the  electric  current. 

It  is  well  known  that  ozone  also  arises  as  a  by-product 
during  the  slow  oxidation  of  phosphorus.  An  idea  can  be 
formed  of  this  process  by  the  following  explanation  :  during 
the  slow  oxidation  only  one  of  the  two  atoms  of  the  oxygen 
molecule  enters  into  combination  with  the  phosphorus ;  and 
the  other  attaches  itself  to  an  undecomposed  molecule  of 
oxygen. 

It  may  be  seen  from  the  above  that  the  third  oxygen  atom 
in  the  ozone  molecule,  which  causes  the  powerful  oxidations, 
can  have  no  other  properties  than  that  of  nascent  oxygen.  In 
fact  it  can  be  proved  that  wherever  slow  oxidation  occurs, 
a  part  of  the  oxygen  acquires  'active  qualities,'  and  acts  in 
the  same  way  as  the  ozone  formed  during  slow  oxidation  of 
phosphorus.  We  cannot  expect  that  ozone  should  be  formed 
when  oxidizable  substances  are  present,  as  these  fix  the  nascent 
oxygen  atom  before  it  can  unite  with  a  molecule  of  oxygen 
to  form  one  of  ozone. 

It  is  with  such  conditions  that  we  have  to  deal  in  the 
1  Clausius,  PoggendorfPs  Annul.,  vol.  cxxi.  p.  250:  1864. 


250  LECTURE    XVII 

organism,  and  for  these  reasons  ozone  is  never  formed  in  the 
body,  though  we  meet  with  energetic  processes  of  oxidation. 
Ä  priori  there  is  no  point  in  trying  to  trace  ozoüe  in  the 
animal  body.  Many  liters  of  oxygen  containing  ozone  might 
be  introduced  into  the  blood,  and  yet  we  could  not  pump  out 
a  single  molecule  of  ozone. 

The  following  experiments  show  that  some  of  the  oxygen 
atoms  attain  '  active  properties '  during  slow  oxidation  by 
ordinary  oxygen. 

If  ammonia  be  present  during  the  oxidation  of  pyrogallol 
in  alkaline  solution  by  atmospheric  oxygen,  it  becomes  oxidized 
into  nitrous  acid.^  Peroxid  of  hydrogen  is  formed  during  the 
oxidation  of  benzaldehyde.^  If  metallic  sodium  be  oxidized  by 
air  in  the  presence  of  petroleum-ether,  the  hydrocarbons,  which 
compose  the  latter,  are  converted  into  the  corresponding  alco- 
hols and  acids. ^ 

It  is  well  known  that  benzol  cannot  be  converted  into 
phenol  by  the  action  of  the  ordinary  oxidizing  agents,  but  that 
it  can  by  means  of  ozone.^  It  can  however  be  done  by  ordinary 
oxygen,  if  ferrous  or  cuprous  sulphate  are  present.^  We  must 
imagine  that  the  suboxid  fixes  one  of  the  two  oxygen  atoms, 
while  the  one  set  free  oxidizes  the  benzol. 

Palladium-hydrogen  has  the  same  eifect  as  the  suboxid 
of  iron  or  copper.  Graham  has  shown  that,  if  palladium  foil 
be  employed  as  the  negative  electrode  in  the  electrolysis  of 
water,  no  hydrogen  is  developed  at  this  pole.  The  hydrogen 
unites  with  the  palladium.  The  metal  takes  up  nine  hundred 
times  its  volume  of  the  gas,  while  at  the  same  time  its  own 
volume  increases.  This  combination  gradually  liberates  a  part 
of  the  hydrogen  ;  it  behaves  like  nascent  hydrogen.  When 
therefore  the  palladium-hydrogen  comes  in  contact  with  atmos- 
pheric oxygen,  the  hydrogen  becomes  oxidized,  a  part  of  the 
oxygen  is  rendered  '  active,^  and  if  benzol  is  present,  it  is  con- 
verted into  phenol,  as  it  would  be  by  ozone.*^ 

^  This  experiment  of  Baumann's  was  communicated  by  Hoppe-Seyler,  Ber.  d. 
deutsch,  ehem.  Ges.,  vol.  xii.  p.  1553  :  1879. 

2  Radenowitsch,  Ber.  cl.  deutsch,  ehem.  Ges.,  p.   1208:  1873. 

3  Hoppe-Seyler,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  xii.  pp.  1553,  1554:  1879. 

*  Nencki  and  P.  Giacosa,  Zeitschr.  f.  physiol.  Chem.,  vol.  iv.  p.  339  :  1880. 
Leeds  {Ber.  d.  deutsch,  ehem.  Ges.,  vol.  xiv.  p.  975:  1881)  could  not  confirm 
this  statement;  in  his  experiments,  the  benzol  was  oxidized  into  carbonic  acid, 
oxalic  acid,  formic  acid,  and  acetic  acid.  But  the  conditions  under  which  the 
experiments  were  carried  out  differed  in  the  two  cases. 

5  Nencki  and  Sieber,  Journ.  f.  prakt.  Chem.,  vol.  xxvi.  pp.  24,  25  :  1882. 

"Hoppe-Seyler,  Zeitschr.  f.  physiol.  Chem.,  vol.  ii.  p.  22:  1878;  and  vol.  x. 
p.  35:  1886;  Ber.  d.  deutsch,  chem.  Ges.,  vol.  xii.  p.  1551:  1879;  and  vol.  xvi. 
pp.  117,  1917:  1883.  Compare  also  Leeds,  ibid.,  vol.  xiv.,  p.  975:  1881;  and 
Moritz  Traube,  ibid.,  vol.  xv.  p.  659 ;  vol.  xvi.  pp.  123,  1201 :  1883 ;  and  vol. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  251 

Nascent  oxygen,  as  might  ä  p)-iori  be  assumed,  acts  as  a 
more  energetic  oxidizer  even  than  ozone.  Ozone,  for  instance, 
cannot  oxidize  free  nitrogen,  any  more  than  it  can  carbonic 
oxid.  The  nascent  oxygen,  on  the  other  hand,  arising  from 
the  action  of  palladium-hydrogen  on  ordinary  oxygen,  oxidizes 
free  nitrogen  to  nitrous  acid,  and  carbonic  oxid  to  carbonic 
acid.^ 

If  benzol  is  introduced  into  our  body,  it  mostly  reappears  in 
the  urine  as  phenol.^  We  may  therefore  assume  that  reducing 
substances  also  occur  in  our  tissues,  and  play  a  part  similar  to 
that  taken  by  them  in  the  above-mentioned  experiments  with 
palladium-hydrogen  or  the  metallic  suboxids.  I  have  already 
stated  (pp.  244,  247)  that  such  reducing  substances  are 
found  in  the  blood  of  asphyxiated  animals ;  and  they  are 
moreover  to  be  met  with  in  all  tissues.  Ehrlich^  showed 
that  blue  coloring  matters,  as  alizarin  blue,  indopheuol  blue, 
lose  their  color  in  the  tissues  of  living  animals,  and  that  the 
tissues  turn  blue  again  on  contact  with  the  air.  We  may 
assume  that  these  readily  oxidizable  reducing  substances  arise 
by  fermentative  action  from  the  food-stuffs  along  with  other 
products  of  decomposition  that  are  not  readily  oxidizable. 
But  as  soon  as  the  readily  oxidizable  substances  become  oxi- 
dized by  the  inspired  oxygen,  a  part  of  the  oxygen  attains 
'  active '  properties,  and  oxidizes  those  which  are  not  readily 
oxidizable. 

That  reducing  substances  do  arise  by  fermentative  action 
in  the  cells,  may  be  seen  in  butyric  acid  fermeutation.  The 
hydrogen  liberated  in  this  process  becomes  oxidized  by  ordi- 
nary oxygen  to  form  water.  Hydrogen  never  proceeds  from 
fermentative  processes,  if  there  has  been  a  sufficient  access  of 
air.*  This  explains  the  absence  of  hydrogen  in  the  atmosphere 
in  spite  of  the  extensive  processes  of  fermentation  going  on  all 
over  the  surface  of  the  earth. 

The  formation  of  saltpeter  shows  us  moreover  in  a  very 

xviii.  pp.  1877-1900 :  1885 ;  also  Baumann  and  Preusse,  Zeitschr.  f.  pliysiol. 
Chem.,  vol.  iv.  p.  453:  1880;  Nencki,  Journ.f.  prakt.  Chem.,  vol.  xxiii.  p.  87: 
1880;  and  Baumann,  Zeitschr.  f.  physiol.  Chem.,  vol.  v.  p.  244:  1881;  and  Ber. 
d.  deutsch,  chem.  Ges.,  vol.  xvi.  p.  2146:  1883.  Moritz  Traube  has  raised  objec- 
tions of  considerable  weight  to  the  theory  that  oxygen  is  rendered  active  by 
reducing  substances.  I  have  given  this  theory  in  my  account,  but  must  expressly 
state  that  it  may  involve  hypotheses  and  analogical  inductions  from'  facts  which 
possibly  are  capable  of  a  diflerent  interpretation.  The  reader  may  form  his  own 
judgment  from  the  interesting  and  instructive  works  quoted  above. 

^  Baumann,  Zeitschr.  f.  physiol.  Chem.,  vol.  v.  p.  244  :  1881. 

2  Schnitzen  and  Naunyn,  Reichert  and  Du  Bois'  Arch.,  p.  349 :  1867. 

^P.  Ehrlich,  "Das  Sauerstoif  bedürfniss  des  Organismus":  Berlin,  1885. 

*  Hoppe-Seyler,  Pflüger's  Arch.,  vol.  xii.  p.  16:  1876;  Zeitschr.  f.  physiol. 
Chem.,  vol.  viii.  p.  214  :  1884. 


252  LECTURE   XVII 

remarkable  way,  how  processes  of  oxidation  may  go  on  in  a 
most  energetic  manner  at  the  same  time  as  processes  of  decom- 
position produced  by  putrefactive  organisms.  Nitrogen,  which 
has  but  a  slight  affinity  for  oxygen,  is  raised  to  the  highest 
stage  of  oxidation  by  the  oxygen-atoms  which  are  liberated 
during  the  oxidation  of  the  reducing  putrefactive  products 
and  which  oxidize  the  ammonia  resulting  from  the  decom- 
position. Recent  researches  have  proved  that  certain  living 
putrefactive  organisms  take  an  active  part  in  the  formation  of 
saltpeter.^ 

It  is  probable  that  all  the  cells  in  our  bodies  have  the  same 
power  as  these  unicellular  beings,  these  organisms  associated 
with  fermentation  and  decomposition.  But  we  need  not 
assume  that  the  reducing  substances  formed  by  them  are 
always  the  same.  Hoppe-Seyler  ^  is  of  opinion  that  hydrogen 
is  liberated  in  the  tissues  of  the  animal  body  just  as  it  is  in 
certain  unicellular  putrefactive  organisms.  That  the  hydrogen 
cannot  be  detected  m  the  tissues  is  no  argument  against  this 
view.  But,  however  this  may  be,  the  nascent  hydrogen  need 
not  be  the  only  reducing  substance  by  means  of  which  active 
oxygen  arises  in  our  tissues.  These  reducing  substances  may 
be  of  very  different  kinds  in  the  various  cells ;  they  may  even 
be  numerous  and  changeable  in  one  and  the  same  cell,  accord- 
ing to  the  functions  it  is  required  to  perform  at  a  given 
moment.^ 

The  '  spontaneous  combustion '  of  hay  affords  a  striking 
example  of  the  activity  which  oxidation  of  the  organic  food- 
stuffs may  attain  when  decomposition  of  the  latter  has  pre- 
viously set  in.  If  hay  is  stacked  before  it  is  thoroughly  dry, 
decomposition  begins  in  the  middle  of  the  damp  stack  through 
the  action  of  organized  or  unorganized  ferments.  As  all 
decomposition  by  ferments  is  accompanied  by  hydration, 
drying  is  the  best  means  of  preventing  it.  Heat  is  liberated 
by  the  decomposition,  and  proportionately  with  the  rise  in 
temperature  in  the  middle  of  the  stack  an  ever-increasing 
accumulation  of  easily  oxidizable  decomposition-products  is 
formed.     If  the  hay  be  now  disturbed  so  that  there  is  free 

^  Muntz  et  Schlösing,  Compt.  rend.,  vol.  Ixxxiv.  p.  301 :  1877  ;  vol.  Ixxxv.  p. 
1018  :  1877  ;  vol.  Ixxxix.  p.  891 :  1879  ;  Warrington,  Chem.  News,  vol.  xxxvi.  p. 
263:  1877;  vol.  xxxix.  p.  224:  1879;  S.  Winogradsky,  Compt.  rend.,  vol.  ex. 
p.  1013 :  1890. 

2  Hoppe-Seyler,  Pfliiger's  Arch.,  vol.  xii.  p.  16:  1876.  Compare  Nencki, 
Journ.  f.  prakt.  Chem.,  vol.  xxiii.  p.  87  :  1880  ;  and  Baumann,  Zeitschr.f.  physiol. 
Chem.,  vol.  v.  p.  244  :  1881. 

^  Compare  Br.  Radziszewski,  "  Zur  Theorie  der  Phosphorescenzerscheinung," 
£er.  d.  deutsch.  Chem.  Ges.,  vol.  xvi.  p.  597  :  1883. 


GASES    OF    THE    BLOOD    AND    EESPIRATION  253 

access  of  atmospheric  oxygen  to  the  internal  parts  of  the  stack, 
the  whole  blazes  up  and  is  consumed/ 

The  rapid  oxidation  of  food-stuffs  which  takes  place  in  our 
tissues  offers  no  mystery  if  the  analogies  that  we  have  dwelt 
upon  are  taken  into  consideration.  We  must  however  not 
forget  that  the  participation  of  active  oxygen  iu  the  process  is 
at  present  only  an  hypothesis,  and  that  the  facts  are  capable  of 
another  explanation. 

The  following  facts  observed  by  me  ^  are  not  explicable 
on  Hoppe-Seyler's  hypothesis.  Certain  intestinal  parasites, 
especially  ascarides,  can  live  and  perform  vigorous  move- 
ments for  several  days  without  oxygen  (compare  Lecture 
XXIII.).  The  kinetic  energy  of  these  movements  can  only 
come  from  processes  of  disintegration,  and  we  should  therefore 
expect,  according  to  Hoppe-Seyler,  that  hydrogen  would  be 
produced  together  with  easily  oxidizable  substances.  This  is 
not  the  case.  The  animals  give  off  a  quantity  of  gas,  which 
can  be  proved  to  consist  of  pure  carbonic  acid,  since  it  is 
entirely  absorbed  by  potash.  No  hydrogen  was  therefore 
formed.  When  I  brought  oxygen  in  contact  with  the  fluid  in 
which  the  worms  had  lived  without  oxygen  for  several  days,  and 
had  during  this  time  carried  out  active  movements,  no  oxygen 
was  absorbed.  We  must  conclude  therefore  that  no  easily 
oxidizable  j^roducts  had  arisen  as  a  result  of  the  disintegrative 
processes. 

Another  hypothesis,  first  started  by  Moritz  Traube,^ 
seems  to  me  therefore  worthy  of  attention.  I  refer  to  the 
idea  that  '  oxygen-carriers '  are  the  active  factors  in  the 
chemical  processes  of  our  body.  By  this  term  are  meant 
substances  which  combine  loosely  with  oxygen  and  readily  give 
it  up  to  others  which  do  not  directly  unite  with  oxygen.  A 
well-known  example  of  such  an  oxygen  transport  is  seen  in  the 
part  played  by  nitric  oxid  in  the  preparation  of  sulphuric  acid. 
Sulphurous  acid  cannot  unite  with  oxygen  directly.  But  if 
nitric  oxid  be  present,  sulphuric  acid  results  ;  for  the  former 
body  forms  a  loose  compound  with  oxygen,  and  gives  up  the 
oxygen  to  the  sulphurous  acid.  A  small  quantity  of  nitric 
oxid  is  capable  of  converting  an  unlimited  quantity  of  sul- 
phurous into  sulphuric  acid. 

A  similar  action  to  that  of  nitric  oxid  in  the  oxidation  of 

1  This  process  so  long  known  to  farmers  has  recently  been  the  subject  of 
numerous  chemical  investigations.  A  summary  of  these  experiments  will  be 
found  in  the  Chem.  Centralbl.,  p.  316,  year  17:  1886.  Compare  also  Th.  Schlös- 
ing,  Compt.  rend.,  vol.  cvi.  p.  1293  :  1888,  and  vol.  cviii.  p.  527 :  1889. 

-  G.  Bunge,  Zeitschr.  f.  physiol.  Chem.,  vol.  xiv.  p.  318  :  1890. 

3  M.  Traube,  "Theorie  der  Fermentwirkungen":  Berlin,  1858. 


254  LECTURE    XVII 

sulphurous  acid  is  manifested  by  sulphindigotate  of  potassium 
in  the  oxidation  of  grape-sugar.  If  a  sohition  of  grape-sugar 
be  heated  in  the  presence  of  air  with  some  carbonate  of  soda, 
only  a  very  insignificant  and  unimportant  absorption  of  oxygen 
takes  place.  But  if  sulphindigotate  of  potassium  be  present,  it 
gives  up  its  loosely  combined  atom  of  oxygen  to  the  grape- 
sugar  and  becomes  decolorized.  On  shaking  up  the  solution 
with  air  it  again  becomes  blue  ;  the  sulphindigotate  of  potassium 
has  again  taken  up  oxygen  from  the  air.  On  letting  the  solution 
stand  for  a  brief  period  it  again  becomes  decolorized.  The  blue 
color  remains  permanent  only  at  the  surface,  where  the  solution 
continues  in  constant  contact  with  the  air.  In  this  manner  a 
small  quantity  of  sulphindigotate  of  potassium  is  able  to  effect 
the  oxidation  of  large  quantities  of  grape-sugar,  provided  a  free 
admission  of  atmospheric  air  be  allowed. 

The  same  result  can  also  be  produced  by  cupric  oxid.  A 
blue  ammoniacal  solution  of  cupric  oxid  is  decolorized  when 
heated  with  grape-sugar.  The  cupric  oxid  is  reduced  to 
cuprous  oxid  ;  it  has  given  up  one  atom  of  oxygen  to  the 
grape-sugar.  On  shaking  it  up  with  air  it  again  becomes  blue, 
and  so  on.  The  cuprous  oxid  here  plays  the  same  part  as 
oxygen-carrier  that  the  nitric  oxid  does  in  the  formation  of 
sulphuric  acid. 

The  oxidation  of  oxalic  acid  in  the  presence  of  a  salt  of  iron 
affords  another  example.  Under  the  influence  of  light,  oxalic 
acid  is  oxidized,  carbonic  acid  is  formed,  while  the  ferric  oxid 
is  reduced ;  the  admission  of  air  causes  the  ferrous  oxid  thus 
formed  again  to  absorb  oxygen  ;  and  thus  a  small  amount  of 
ferric  salt  has  the  power  of  gradually  causing  the  oxidation  of 
a  large  quantity  of  oxalic  acid.^  A  similar  part  may  possibly 
be  played  by  the  iron  in  our  tissues,  since  this  substance  is 
present  in  loose  combination  wherever  proteid  and  nuclein  are 
to  be  found. 

A  familiar  example  of  this  carriage  of  oxygen  is  to  be 
seen  in  the  oxidation  by  means  of  atmospheric  oxygen  of 
methyl  and  ethyl  alcohol  vapors  to  formic  and  acetic  acids,  in 
the  presence  of  finely  divided  platinum,  e.  g.,  spongy  platinum. 
Here  also  we  might  consider  the  metal  as  an  oxygen  carrier, 
though  chemists  are  generally  content  to  speak  more  vaguely  of 
a  '  contact  effect.'  Many  attempts  have  been  made  to  show 
that  in  this  process  the  platinum  could  be  replaced  by  organic 
substances,  by  '  ferments.'  It  is  still  undecided  however 
whether  organized  ferments  may  not  have  been  responsible  for 
all  these  fermentative  processes,  as  e.  g.,  the  mycoderma  aceti  in 

1  Pfeffer,  Unlcrs.  aus  dem  botan.  Institut  zu  l'übingcn,  vol.  i.  p.  679  :  1885. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  255 

the  rapid  process  of  vinegar-making.  We  cannot  however 
exclude  the '  possibility  that  unorganized  ferments  may  also 
effect  the  oxidation.  We  have  already  seen  how  the  same 
result  may  be  produced  by  a  metal,  an  organic  substance  or  a 
living  cell.  In  the  same  way  ferments  might  be  the  oxygen 
carriers  in  our  tissues.  They  must  however  be  much  more 
energetic  in  their  action  than  the  mycoderma  aceti,  since 
alcohol  is  oxidized  in  our  body  to  its  end-products,  carbonic 
acid  and  water,  and  does  not  stop  at  the  stage  of  acetic  acid. 
We  should  have  to  assume  the  presence  in  our  tissues  of  fer- 
ments which,  in  the  shortest  possible  time,  converted  fats,  car- 
bohydrates, and  proteids  into  their  end-products,  carbonic  acid, 
water,  urea,  and  sulphuric  acid. 

The  theory  of  the  presence  of  active  oxygen  in  the  tissues 
has  also  been  shown  to  be  at  variance  with  the  fact  that  certain 
very  readily  oxidizable  substances  remain  wholly  or  partially 
unaltered  in  their  passage  through  the  tissues  of  our  body,  such 
as  pyrogallol,^  pyrocatechin,^  and  phosphorus.^  Carbonic  oxid  * 
which  is  converted  into  carbonic  acid  by  nascent  oxygen,  and 
oxalic  acid  which  is  so  readily  oxidizable,^  are  quite  unaltered 
in  the  organism. 

But  these  facts  too  may  be  explained  in  another  way. 
Every  molecule,  while  on  its  travels,  does  not  necessarily  reach 
that  point  where  it  would  meet  with  nascent  oxygen.  It  even 
appears  a  plausible  assumption  that  substances  which  do  not 
belong  to  normal  nutrition,  or  such  as  are  poisonous,  do  not 
reach  those  cells  in  which  the  most  intense  oxidation  occurs,  to 
constitute  a  source  of  energy  for  the  performance  of  normal 
functions.  These  cells,  like  all  others,  make  their  choice ;  they 
work  with  definite  material,  and  reject  that  which  is  likely  to 
be  injurious. 

Another  explanation  of  the  fact  that  pyrogallol  and  pyro- 
catechin  do  not  become  oxidized,  is  that  they  do  not  circulate 
in  a  free  state  through  the  body,  but,  like  all  hydroxyl  deriva- 
tives   of   the    aromatic  hydrocarbons,    i.  e.,  all  phenols,   com- 

^  CI.  Bernard,  "  Lecons  sur  les  proprietes  physiologiques,  &c.,  des  liquides  de 
I'organisme,"  vol.  ii.  p.  144 :  1859;  Baiimann  and  Herter,  Zeitschr.  f.  physioL 
Chem.,  vol.  i.  p.  249  :  1877. 

2  Baumann  and  Herter,  ihicl.,  p.  249. 

3  Hans  Meyer,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xiv.  p.  329  :  1881.  The 
previous  literature  on  this  subject  will  be  found  quoted  here. 

*  Gaetano  Gaglio,  ibid.,  vol.  xxii.  p.  236  :  1887.  In  Gaglio's  experiments  the 
carbonic  oxid  was  inspired.  St.  Zaleski  (ibid.,  vol.  xx.  p.  34 :  1885)  found  that, 
after  intraperitoneal  injection  of  carbonic  oxid  blood,  no  carbonic  oxid  was 
given  out  by  the  lungs.  It  thus  appears  that  carbonic  oxid,  introduced  in  this 
way,  becomes  oxidized. 

5  Gaglio,  loc.  cit.,  p.  246. 


256  LECTURE    XVII 

bine  with  the  sulphuric  acid  which  arises  from  tlie  decomposi- 
tion of  the  proteids  in  the  tissues.  The  phenols  play  the  same 
part  here  that  the  alcohols  do  in  the  formation  of  the  sulphuric 
ethers.  A  union  accompanied  by  dehydration  takes  place ;  the 
sulphuric  acid  is  converted  from  a  dibasic  into  a  monobasic 
acid,  and  reappears  in  the  urine  as  an  alkaline  salt. 

These  conjugated  sulphuric  acids  were  discovered  by  Bau- 
mann. He  showed  that  the  urine  of  herbivora  always  contains 
an  abundance  of  phenolsulphate  of  potassium.^  Together  with 
this  another  conjugated  sulphuric  acid  occurs,  in  which  the 
phenol  is  replaced  by  a  methylated  phenol  called  cresol,^  and 
also  sulphuric  acid  conjugated  with  pyrocatechin  ^  and  with 
indoxyl.^  These  combinations  were  also  found  to  be  invariably 
present  in  human  urine,  and  only  absent  in  the  urine  of  Car- 
nivora if  nothing  but  meat  were  eaten.  If  however  phenol  be 
administered  to  dogs,  it  appears  in  the  urine  as  the  corresponding 
conjugated  sulphate  (compare  Lectures  XXI.  and  XXII.). 

It  seems  that  sulphuric  acid  which,  being  the  extreme  stage 
of  oxidation  of  sulphur,  is  not  capable  of  further  oxidation,  also 
protects  the  organic  conjugate  against  oxidation,  even  if  the 
latter  belongs  to  the  group  of  fats.  Salkowski  ^  found  that 
ethylsulphuric  acid,  when  given  to  a  dog,  passed  unaltered  into 
the  urine. 

The  question  whether  the  nucleus  of  benzol  is  ever  broken 
up  by  the  decomposing  and  oxidizing  agents  occurring  in  our 
tissues,  has  not  yet  been  settled.  All  aromatic  compounds, 
whose  behavior  in  the  animal  body  has  been  examined  in 
detail,  reappear  in  the  urine  as  aromatic  compounds,  although 
mostly  in  an  altered  form.  Thus  it  is  certain  that  benzoic  and 
salicylic  acids,  when  introduced  into  the  body,  can  be  entirely 
recovered  from  the  urine,  either  unaltered  or  combined  with 
glycin  to  form  hippuric  acid  or  salicyluric  acid  respectively.® 
(Compare  Lecture  XIX.)  But  the  experiments  with  other  aro- 
matic compounds  have  not  been  executed  quantitatively.  The 
possibility  remains  that  at  least  a  small  part  is  decomposed. 
Outside  the  organism,  benzol  can  be  oxidized  by  the  action  of 
ozone  at  an  ordinary  temperature,  and  thus  converted  into 
carbonic   acid,  oxalic   acid,  formic    acid,  acetic   acid,   and  an 

1  Baumann,  Pflüger's  Arch.,  vol.  xii.  p.  69  :  1876  ;  and  vol.  xiii.  p.  285  :  1876. 

2  C.  Preusse,  Zeitscltr.  f.  physiol.  Cheni.,  vol.  ii.  p.  355:  1878;  and  Brieger, 
iUd.,  vol.  iv.  p.  204  :  1880. 

^  Baumann,  Pflüger's  Arch.,  vol.  xii.  p.  63  :  1876. 

■*  Baunaannand  L.  Brieger,  Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  254:  1879. 
5  E.  Salkowski,  Pflüger's  Arch.,  vol.  xii.  p.  63  :  1876. 

^  W.  V.  Schröder,  Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  327:  1879;  U.  Mosso, 
Arch.f.  exper.  Path.  u.  Pharm.,  vol.  xxvi.  p.  267  :  18S9. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  257 

amorphous  black  residue.^  Should  a  really  active  oxygen  be 
demonstrated  as  existing  in  our  tissues,  we  might  infer  that  a 
complete  decomposition  of  the  benzol  would  also  occur  in 
them. 

Phenol  is  oxidized  and  split  up  by  permanganate  of 
potassium  in  an  alkaline  solution,  with  the  production  of 
oxalic  acid.  This  fact  led  Salkowski  ^  to  examine  the  blood 
of  rabbits  poisoned  by  phenol  for  oxalic  acid.  Oxalic  acid  was 
detected  in  two  out  of  three  cases,  but  not  in  the  blood  of  two 
healthy  rabbits. 

Experiments  carried  out  by  Tauber^  and  Auerbach*  in 
Salkowski's  laboratory  and  by  SchafFer  ^  in  Nencki's  laboratory, 
showed  equally  that  if  phenol  be  given  to  dogs,  only  a  part, 
varying  from  30  to  70  per  cent,  according  to  the  amount  intro- 
duced, ever  reappears  in  the  urine  and  feces.  But  it  should 
not  be  immediately  assumed  that  the  phenol  which  has  dis- 
appeared, has  undergone  combustion.  It  is  quite  possible  that 
the  benzol  was  not  destroyed,  but  that  the  phenol  had  passed 
into  another  aromatic  compound.  Schaifer  in  fact  found,  in 
two  experiments  in  which  he  estimated  the  amount  of  conju- 
gated sulphuric  acids,  that  these  latter  were  increased  after  the 
addition  of  phenol,  and  in  the  exact  ratio  of  the  amount  of 
phenol  administered.  No  increase  of  oxalic  acid  in  the  urine 
could  be  detected  in  these  experiments,  nor  in  those  of  Tauber 
and  Auerbach.  Nor  was  the  latter  able  to  find  any  oxalic  acid 
in  the  blood. 

After  Schotten  ^  and  Baumann  ^  had  introduced  certain 
aromatic  amido-acids,  with  three  carbon  atoms  in  the  side- 
chain  (tyrosin,  phenylamidopropionic  and  amidocinnamic  acids), 
into  the  organism  of  men,  dogs,  and  rabbits,  they  could  find  no 
increase  of  any  known  aromatic  compound  in  the  urine.  Hence 
they  concluded  that  these  aromatic  compounds  had  been  com- 
pletely oxidized.^ 

Finally  N.  Juvalta^  has  shown  by  careful  quantitative 
experiments  that  phthalic  acid  is  in  great  part  destroyed  in  the 

'  Leeds,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  xiv.  p.  975  :  1881. 

2  Salkowski,  Pfliiger's  Arch.,  vol.  v.  p.  357  :  1872. 

3  Tauber,  Zeitschr.  f.  physiol.  Chem.,  vol.  ii.  p.  366  :  1878. 
■*  Auerbach,  Virchow's  Arch.,  vol.  Ixxvii.  p.  226  :  1879. 

5  Schaflfer,  Journ.  f.  prakt.  Chem.,  N.  F.,  vol.  xviii.  p.  282  :  1878. 

*  Schotten,  Zeitschr.  f.  physiol.  Chem.,  vol.  vii.  p.  23  :  1882 ;  and  vol.  viii.  p. 
60:  1883. 

'Baumann,  ihid.,  vol.  x.  p.  130  :  1886.  Compare  also  K.  Baas,  ibid.,\o\. 
xi.  p.  485  :  1887. 

^  Vide  also  Nencki  and  P.  Giacosa,  ibid.,  vol.  iv.  p.  328  :  1880. 

^N.  Juvalta  (Bunge's  laboratory),  Zeitschr.  f.  physiol.  Chem.,  vol.  xiii.  p. 
26  :  1888. 

17 


258  LECTURE    XVII 

organism  of  dogs.  Of  22.4  grms.  which  had  been  introduced 
into  the  stomach,  only  7  grms.  reappeared  in  the  urine  and 
feces.     No  other  aromatic  compounds  were  to  be  found. 

What  is  actually  known  concerning  the  changes  which 
aromatic  compounds  undergo  through  oxidation  in  the  animal 
body  is  as  follows  : 

The  hydrocarbons  are  hydroxylized,  the  benzol  being  con- 
verted into  oxybenzol  and  dioxybenzoP — hydrochinon  and  pyro- 
catechin.  Oxidation  does  not  advance  a  step  further  ;  for,  after 
the  administration  of  a  few  milligrammes  of  dioxybenzol  (pyro- 
catechin),  it  reappears  unaltered  in  the  urine.^ 

If  the  aromatic  combination  introduced  into  the  animal 
body  has  a  side-chain  belonging  to  the  fat-group,  it  is  in  most 
cases  attacked  by  oxygen.^  Thus  toluol  (CgH,— CHg),  ethyl- 
benzol  (CgHg— CjHj),  propylbenzol  (C^H.— CgH^),  benzylalcohol 
(CgHg— CH.,OH),  are  all  converted  by  oxidation  into  benzoic 
acid  (CgH.COOH).  On  the  contrary,  phenylacetic  acid  (CgH^ — 
CH2— COÖH)  is  not  attacked  by  oxygen.  The  inoxidizable 
carboxyl  group  appears  in  this  case  to  protect  the  adjoining 
carbon  atom  in  the  same  way  as  we  have  seen  happen  in  the 
inoxidizable  sulphuric  acid.  Group  CHg  in  phenylacetic  acid 
is  protected  on  one  side  by  the  indestructible  benzol  ring,  on 
the  other  by  carboxyl.  But  if  more  than  one  atom  of  carbon 
is  inserted  between  the  benzol  ring  and  carboxyl,  this  protec- 
tion does  not  suffice.  Phenylpropionic  acid  (CgH^ — CHg — 
CH2-COOH)  and  cinnamic  acid  (CgH,-CH=CH-COOH) 
are  converted  into  benzoic  acid  (CgHgCOOH)  by  oxidation.  If 
more  than  one  side-chain  be  present  of  the  benzol  nucleus, 
only  one  of  them  is  converted  by  oxidation  into  carboxyl. 
Thus  the  following  changes  are  produced  by  oxidation  : — 

f  PIT    "1  r  OTT       1 

Xylol,  CgHi  i  QfT^    >  is  converted  into  CgH^  <  qqAjx  \  toluylic  acid. 

fCHS  rCH3     ] 

Mesitylene,    CgHo^CHa   V         "  "        CgHä -^  CH.,      V  mesity lerne  acid. 

[CHs  j  iCOOHJ 

Cymol,  CgH,  |  g»^'  |  "  "         CeH,  {  g^'jj  }  cuminic  acid. 

In  the  animal  body  many  aromatic  compounds  enter  into 
combination  with  members  of  the  fat-group  which  are  easily 
oxidizable,  and  protect  these  from  oxidation.     The  best-known 

*  Baumann  und  C.  Preusse,  Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  156  : 
1879. 

2  De  Jonge,  ibid.,  vol.  iii.  p.  184  :  1879. 

*  Schnitzen  und  Naunyn,  Reichert  and  Du  Bois'  Ar-ch.,  p.  349  :  1867 ;  Nencki 
and  P.  Giacosa,  Zeitschr.  f.  physiol.  Chem.,  vol.  iv.  p.  325  :  1880. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  259 

instance  of  this  kind  is  the  formation  of  hippuric  acid  from 
glycocol  and  .benzoic  acid — 

I  +1=1  +HA 

COOH  COOH  COOH 

When  no  aromatic  compounds  are  present  in  the  animal  body, 
glycocol  undergoes  complete  oxidation,  and  is  converted  into 
carbonic  acid,  water,  and  urea  (see  Lecture  XIX.) ;  but,  by 
uniting  with  the  indestructible  benzoic  acid,  it  is  protected 
against  the  influence  of  oxygen,  and  appears  in  the  urine  as 
hippuric  acid  (see  Lecture  XIX.). 

Schmiedeberg  and  his  pupils  ^  have  observed  an  interesting 
synthetic  process  of  this  kind  in  which  a  product  of  the  oxida- 
tion of  sugar  unites  with  an  aromatic  compound,  and  is  thus 
protected  against  further  decomposition  and  oxidation.  If 
camphor  (Cj^HjgO)  be  administered  to  a  dog,  this  substance 
is  hydroxylized  in  the  same  way  as  we  have  seen  happen  with 
regard  to  benzol ;  and  campherol  [Cj(,Hjg(OH)0]  is  formed. 
But  this  product  does  not  pass  as  such  into  the  urine,  but  com- 
bined with  glycuronic  acid,  with  which  it  has  united  with 
dehydration.  The  formula  of  glycuronic  acid  is  CgHj^O^  and, 
judging  from  all  its  properties  and  reactions,  it  must  be  regarded 
as  a  derivative  of  grape-sugar,  and  as  a  result  of  incipient 
oxidation.^  If  we  break  up  the  compound  of  campherol  and 
glycuronic  acid  by  boiling  with  dilute  acids,  the  liberated 
glycuronic  acid  is  rapidly  decomposed ;  it  becomes  brown,  and 
carbonic  acid  is  developed.  It  is  difficult  to  obtain  a  satisfactory 
quantity  undecomposed  for  analysis.  The  ease  with  which  this 
acid  is  decomposed  and  oxidized  explains  why  we  do  not  meet 
with  it  in  the  normal  metabolism  of  animals.  Here  we  find 
that  the  sugar,  as  soon  as  its  oxidation  has  commenced,  is 
rapidly  decomposed  into  carbonic  acid  and  water.  It  appears 
that  fats  offer  definite  points  of  attack  for  oxygen  ;  and  if  these 
points  are  protected  by  non-oxidizable  substances,  the  oxygen 
is  unable  to  operate  upon  them.  As  soon  as  these  points  are 
undefended,  they  are  rapidly  decomposed  and  oxidized. 

Schmiedeberg  ^  has  met  with  glycuronic  acid  a  second  time 
under  different  circumstances.  He  fed  a  dog  on  food  contain- 
ing  no   proteid,  such    as   bacon  and   starch   paste,  and   then 

^  C.  Wiedemann,  Arch.  f.  exper.  Path.  u.  Pharm,,  vol.  vi.  p.  230  :  1877 ; 
Schmiedeberg  and  Hans  Meyer,  Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  422  :  1879. 

2  On  the  chemical  properties  of  glycuronic  acid,  vide  H.  Thierfelder,  ibid., 
vol.  li.  p.  388  :  1887. 

'  Schmiedeberg,  Arch.  f.  exper.  Path,  u.  Pharm.,  vol.  xiv.  pp.  306,  307  :  1881. 


260  LECTURE    XVII 

administered  benzol.  In  order  to  form  phenolsulphuric  acid, 
the  organism  in  this  case  had  at  its  disposal  only  a  minute 
quantity  of  sulphuric  acid,  resulting  from  the  decomposition 
of  proteids  in  the  tissues — no  sulphur  having  been  introduced 
with  the  food.  It  follows  that  all  the  phenol  formed  from  the 
benzol  did  not  appear  in  the  urine  conjugated  with  sulphuric 
acid.  It  was  proved  that  a  part  appeared  as  conjugated  glycu- 
ronic  acid. 

Other  inquirers  have  also  repeatedly  met  with  glycuronic 

acid.  Jaffe  ^  found  that  orthonitroluol  |  CgH^  <  pxr^ ) 
is  converted,  in  the  dog,  into  orthonitrobenzyl  alcohol 
lCgH^<  PTT^OTtI  This  alcohol  appears  in  the  urine  con- 
jugated with  an  acid,  which  seems  to  be  identical  with 
Schmiedeberg's  glycuronic  acid.  Mering  and  Musculus  ^  found, 
in  the  urine  of  men  and  dogs  to  whom  hydrate  of  chloral  or  of 
butylchloral  had  been  administered,  the  corresponding  alcohols, 
trichlorethylalcohol  and  trichlorbutylalcohol  conjugated  with 
glycuronic  acid.  It  is  to  be  noted  that  in  this  process  the  con- 
jugate of  glycuronic  acid  is  formed  by  reduction,  while  in  the 
processes  observed  by  Schmiedeberg  and  Jaffö,  it  was  due  to 
oxidation.  Again,  in  the  experiments  of  Mering  and  Musculus, 
it  was  not  an  aromatic  compound  which  protected  the  gly- 
curonic acid  from  oxidation,  but  one  belonging  to  the  fatty 
series,  which  had  been  rendered  more  or  less  incombustible  by 
chlorin. 

*  Jaffe,  Zeitschr.f.physiol.  Chem.,  vol.  ii.  p.  47  :  1878. 

*  Von  Mering  and  Musculus,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  viii.  p.  662  : 
1875  ;  von  Mering,  Zeitschr.  f.  physiol.  Chem.,  vol.  vi.  p.  480  :  1882.  Vide  also 
Külz,  Pflüger's  Arch.,  vol.  xxviii.  p.  506  :  1882 ;  and  Kossel,  Zeitschr.  f. physiol. 
Chem.,  vol.  iv.  p.  296:  1880;  and  M.  Lesnik,  Arch.  f.  exper.  Path.  u.  Pharm., 
vol.  xxi.  p.  168:  1887. 


LECTURE   XVIII 

THE    GASES    OF    THE    BLOOD    AND    RESPIRATION    (continued) 

BEHAVIOR   OF    CARBONIC   ACID    IN   THE    PROCESSES 
OF    INTERNAL    AND    EXTERNAL    RESPIRA- 
TION  CUTANEOUS    RESPIRATION 

INTESTINAL   GASES 

In  our  previous  remarks  on  the  gases  of  the  blood  and  on 
respiration  we  have  become  acquainted  with  the  behavior  of 
oxygen  and  the  processes  of  oxidation  in  the  tissues.  It  now 
only  remains  for  us  to  consider  the  ultimate  gaseous  product 
of  the  processes  of  oxidation  and  decomposition,  carbonic  acid, 
together  with  its  behavior  in  the  processes  of  internal  and 
external  respiration. 

In  the  venous  blood  of  the  dog,  the  carbonic  acid  amounts 
to  from  39  to  48  vols,  per  cent,  (reckoned  at  0°  C.  and  760 
mm.  Hg.) ;  in  the  arterial,  to  an  average  of  about  8  vols,  per 
cent,  less.^ 

Carbonic  acid,  like  oxygen,  is  not  simply  absorbed  in  the 
blood,  as  there  is  far  too  large  an  amount.  Water  absorbs 
double  its  own  bulk  from  an  atmosphere  of  pure  carbonic  acid, 
at  0°  C. ;  at  the  temperature  of  a  room,  it  absorbs  its  own 
volume,  and  at  the  temperature  of  the  body,  half  its  volume  or 
50  vols,  per  cent,  of  this  gas.  Very  nearly  as  much  as  this  is 
contained  in  venous  blood.  If  therefore  the  carbonic  acid  were 
simply  absorbed,  its  partial  pressure  would  amount  to  a  whole 
atmosphere.  This  cannot  be  the  case,  for  the  partial  pressures 
of  all  the  gases  of  the  blood  together  can  never  amount  to 
much  over  an  atmosphere. 

The  partial  pressure  of  the  carbonic  acid  in  the  blood  is 
accurately  known  from  the  researches  of  Pflüger  and  his  pupils 
Wolflfberg,^  Strassburg,^  and  Nussbaum.^  They  introduced 
blood  from  the  vessels  of  a  living  dog  into  the  upper  end  of  a 

■*  A.  Sehöflfer,  Wien.  akad.  Sitzungsher.,  vol.  xli.  p.  589:  1860;  Sczelkow, 
ibid.,  vol.  xlv.  p.  171  :  1862. 

2  Wolffberg,  Pfliiger's  Arch.,  vol.  iv.  p.  465  :  1871 ;  and  vol.  vi.  p.  23  :  1872. 
^  Strassburg,  ibid.,  vol.  vi.  p.  65  :  1872. 
•*  Nussbaum,  ibid.,  vol.  vii.  p.  296  :  1873. 

261 


262  LECTURE   XVIII 

vertical  glass  tube  which  contained  nitrogen  with  a  small 
percentage  of  carbonic  acid.  The  blood  ran  down  against  the 
sides  of  the  tube  without  coagulating,  and  was  at  once  removed 
when  it  reached  the  lower  end  by  a  particular  arrangement 
which  prevented  any  air  getting  to  it.^  If  the  tension  of  the 
carbonic  acid  in  the  blood  is  greater  than  in  the  gas  inside  the 
tube,  then  the  amount  of  carbonic  acid  in  the  gas  must  increase ; 
if  the  tension  in  the  blood  is  less,  then  the  amount  of  carbonic 
acid  in  the  gas  must  diminish.  It  was  proved  by  numerous 
experiments  that  the  pressure  of  COg  amounts  to  54  per  cent, 
of  an  atmosphere  in  the  blood  of  the  large  veins  of  a  dog  and 
in  that  from  the  right  heart,  and  to  2.8  per  cent,  in  arterial 
blood.^' 

Now,  as  water  at  the  temperature  of  the  body  takes  up 
only  about  50  vols,  per  cent,  of  COg  from  an  atmosphere  of 
pure  carbonic  acid,  it  follows  that  venous  blood,  which  is  under 
a  carbonic  acid  pressure  of  only  5  per  cent,  or  gV  ^^  ^^ 
atmosphere,  cannot  contain  more  than  about  |^  =  2|  vols,  per 
cent,  of  CO2  simply  absorbed.  The  remaining  36  to  46  vols, 
per  cent,  must  be  in  a  state  of  chemical  combination,  and  a 
glance  at  the  composition  of  the  ash  of  blood  shows  us 
that  the  substances,  which  fix  carbonic  acid,  must  be  soda 
and  potash.  The  ash  of  the  plasma  has  never  been  analyzed. 
I  found  that  serum,  the  ash  of  which  cannot  be  of  very  differ- 
ent constitution  from  that  of  the  plasma,  has  the  following 
composition  : — ^ 

One  Thousand  Geammes  of  Serxjm  from  Dog's  Blood  Contains — 


K2O 0.202 

Na^O 4.341 

CaO 0.176 

MgO 0.041 


FeA 0.010 

PA 0.489 

CI 3.961 


We  need  take  no  notice  of  the  minute  proportion  of  potassium, 
which  probably  arises  mostly  from  the  breaking  up  of  the 
leucocytes,  and  of  which  there  is  only  a  trace  in  the  plasma  of 
the  living  blood.  Nor  is  it  necessary  to  take  into  consideration 
the  small  amount  of  lime  and  magnesia ;  they  are  for  the  most 
part  combined  with  the  albumins  and  nucleo-albumins,  and 
perhaps  are  not  at  all  concerned  in  fixing  carbonic  acid. 
Anyhow,  the  bulk  of  the  carbonic  acid  in  the  plasma  is  com- 

^  Diagrams  and  description  of  the  apparatus  are  given  by  Strassburg,  Pflüger 's 
Arch.,  vol.  vi.  p.  69 :  1872. 

2  Strassburg,  loc.  cit. 

3  The  analysis  has  been  published  only  in  part  {Zeitschr.f.  Biolog.,  vol.  xii. 
p.  204:  1876). 


GASES    OF    THE    BLOOD    AND    RESPIRATION  263 

bined  with  sodium  :  3.463  of  the  4.341  grms.  of  sodium  are 
sufficient  to  saturate  the  only  strong  mineral  acid  of  the 
plasma,  the  hydrochloric  acid.  The  remainder,  0.878  grm.  of 
sodium,  is  able  to  fix  0.623  grm.  COg  =316  c.cms.  carbonic  acid 
gas  (computed  at  0°  C.  and  760  mm.  Hg.  pressure),  besides  an 
equal  additional  amount  when  the  bicarbonate  of  soda  is 
formed.  632  c.cms.  of  carbonic  acid  (i.  e.,  63  vols,  per  cent.) 
may  therefore  be  chemically  combined  in  a  liter  of  blood- 
plasma.  It  must  however  be  remembered  that  the  carbonic 
acid  never  really  reaches  quite  63  volumes  per  cent.,  as  the 
0.878  grm.  sodium  must  be  divided  amongst  the  other  weak 
acids — such  as  phosphoric  acid,  proteid,  and  perhaps  many 
others,  each  of  which  is  of  little  importance  singly,  but  which 
altogether  exert  some  influence.  As  a  fact,  from  43  to  57  vols. 
per  cent,  of  carbonic  acid  have  been  found  in  arterial  blood- 
serum  of  the  dog.  The  amount  of  CO2  must  be  still  larger  in 
the  serum  of  venous  blood,  where  the  disposable  sodium  is  perhaps 
almost  completely  saturated  with  carbonic  acid.  How  large  a 
share  of  the  sodium  falls  to  the  lot  of  the  carbonic  acid  depends 
on  '  mass  influence,'  i.  e.,  on  the  partial  pressure  of  the  carbonic 
acid.^  In  the  tissues  where  COg  is  liberated  by  oxidation  and 
decomposition,  and  its  partial  pressure  rises,  sodium  bicarbonate 
must  be  formed  at  the  cost  of  the  sodium  albuminate  and  of 
the  dibasic  sodium  phosphate  (Na2HPOJ,  which  latter  gives 
up  one-half  of  its  sodium  and  is  converted  into  the  acid  salt 
(NaH^POJ.  In  the  alveoli  of  the  lungs,  where  the  partial 
pressure  of  the  carbonic  acid  is  diminished  in  consequence  of 
the  constant  mechanical  ventilation,  the  blood  gives  off  a 
portion  of  its  carbonic  acid  by  diifusion  ;  the  mass-influence  of 
the  CO2  in  the  blood  becomes  lessened,  and  that  of  the  other 
acids  relatively  increased  ;  again  sodium  albuminate  and  dibasic 
sodium  phosphate  (ISTa^HPO^)  are  formed  at  the  cost  of  the 
sodium  bicarbonate.  As  soon  as  the  amount  of  free  carbonic 
acid  decreases,  however  little,  the  amount  of  the  loosely  com- 
bined CO2  also  diminishes,  and  even  to  a  considerable  extent. 
By  this  arrangement  the  amount  of  carbonic  acid  of  the  blood 
can  vary  within  wide  limits  without  the  total  pressure  of  the 
gas  being  materially  altered.  A  change  of  pressure  up  to  2.6 
per  cent,  of  an  atmosphere  produces  an  alteration  of  8  vols,  per 
cent,  in  the  carbonic  acid  of  the  blood.  This  allows  of  large 
quantities  of  CO2  being  transported  in  a  short  time  from  the 
tissues  into  the  lungs. 

1  N.  Zuntz,  Centralbl.  f.  d.  med.  Wissensch.,  p.  527  :  1867;  F.  C.  Bonders, 
Pfliiger's  Arch.,  vol.  v.  p.  20  :  1872.  Vide  also  J.  Gaule,  Du  Bois'  Arch.,  p.  469  : 
1878. 


264  LECTURE    XVIII 

Hoppe-Seyler  and  his  pupil  Sertoli  ^  have  shown  that  proteid 
does  indeed  compete  with  the  carbonic  acid  for  the  possession 
of  the  sodium.  Proteid  drives  out  carbonic  acid  in  a  vacuum 
from  a  solution  of  simple  sodium  carbonate ;  the  amount  driven 
out  is  however  very  small,  as  might  ä  priori  be  anticipated, 
owing  to  the  great  molecular  weight  of  the  proteid.^ 

The  occurrence  of  phosphates  of  the  alkalies  in  the  plasma 
has  frequently  been  doubted.^  The  phosphoric  acid  in  the  ash 
has  been  ascribed  to  the  lecithin  and  nuclein,  but  the  amount 
is  too  large  for  this  purpose,  at  any  rate  in  dog's  blood ;  in 
bullock's  and  pig's  blood  it  is  certainly  much  smaller.^  But, 
at  any  rate,  it  is  only  a  small  portion  of  the  alkalies  which  is 
combined  with  phosphoric  acid  in  the  plasma.  In  the  cor- 
puscles, on  the  contrary,  there  is  no  doubt  that  phosphates  play 
an  important  part  in  fixing  carbonic  acid. 

The  way  in  which  the  phosphoric  acid  is  driven  from  the 
possession  of  the  sodium  by  the  carbonic  acid,  and  vice  versa, 
may  be  demonstrated  by  a  simple  experiment.  If  to  a  solution 
of  NagHPO  a  few  drops  of  litmus  solution  be  added,  the  solu- 
tion becomes  blue.  If  COg  be  now  introduced  the  solution 
becomes  red ;  the  carbonic  acid  is  not  the  cause  of  this  change 
in  color,  as  a  control  experiment  shows,  but  the  formation  of 
NaH2PO^.  NaHCOg  is  formed  simultaneously.  If  the  vessel 
be  left  open,  the  carbonic  acid  gradually  disappears,  the  mass 
influence  of  the  phosphoric  acid  becomes  relatively  greater,  it 
again  takes  possession  of  the  second  sodium  equivalent,  of 
which  it  had  been  robbed  by  the  COg,  and  the  blue  color  reap- 
pears.    This  process  can  be  hastened  by  boiling. 

Carbonic  acid  is  found  not  only  in  the  blood-plasma  but 
also  in  the  corpuscles,  though  not  in  such  large  quantities. 
This  follows  from  the  simple  fact  that  the  total  blood  contains 
less  CO2  than  the  serum.  But  the  difference  is  not  sufficient  to 
enable  us  to  ascribe  all  the  carbonic  acid  to  the  serum.^ 

The  carbonic  acid  cannot  be  completely  removed  from  the 
serum  by  the  air-pump,  a  proof  that  the  amount  of  the  non- 
volatile weak  acids  is  less  than  the  equivalent  of  the  0.9  per 
1000  sodium  just  estimated.  But  more  than  half  can  be 
removed,*'  a  proof  that  the  process  is  not  merely  a  transition 

1  Sertoli,  Hoppe-Seyler's  Med.  chem.  Unters.,  Heft  iii.  p.  350  :  Berlin,  1868. 

2  Hoppe-Seyler,  "Physiologische  Chemie,"  p.  503  :  Berlin,  1879. 
^  Sertoli,  loc.  cit. 

4  Vide  Bunge,  Zeitschr.  f.  Biolog.,  vol.  xii.  pp.  206,  207  :  1876 ;  and  Sertoli, 
loc.  cit. 

*  Alexander  Schmidt,  Berichte  über  die  Verhandlungen,  der  königl.  sächs. 
Ges.  d.  Wissensch.  zu  Leipzig,  Math.  phys.  Classe,  vol.  xix.  p.  30  :  1867. 

ß  Pflüger,  "  üeber  die  Kohlensäure  des  Blutes,"  p.  11  :  Bonn,  1864. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  265 

from  sodium  bicarbonate  into  carbonate,  but  also  a  partial  dis- 
placement of  the  firmly  combined  carbonic  acid  by  the  other 
weak  acids,  proteid,  phosphoric  acid,  &c. 

The  carbonic  acid  may,  on  the  contrary,  be  completely 
pumped  out  of  the  blood.^  And  moreover  Pflüger  ^  has 
shown  that  if  sodium  carbonate  be  added  to  the  blood,  the 
CO2  may  be  driven  out  even  from  this  in  a  vacuum.  In  order 
to  explaia  these  facts,  we  must  assume  either  that  acids  from 
the  corpuscles  diffuse  into  the  plasma,  or  that  sodium  carbonate 
diffuses  from  the  plasma  into  the  corpuscles. 

With  regard  to  the  acids  of  the  blood-corpuscles,  the  most 
important  place  is  held  by  the  phosphoric  acid,  in  which  the 
corpuscles  at  any  rate  are  far  richer  than  the  plasma.  Only  a 
very  small  portion  of  this  large  amount  of  phosphoric  acid  can 
be  contained  in  the  corpuscles  as  an  organic  compound.  In  the 
second  place,  probably  the  oxyhemoglobin  is  of  influence  for, 
as  Preyer  ^  has  shown,  it  drives  out  COg  from  sodium  carbonate 
in  a  vacuum. 

It  has  been  much  disputed  whether  the  giving  off  of  car- 
bonic acid  from  the  capillaries  of  the  lungs  into  the  air  of  the 
alveoli  simply  follows  the  laws  of  diffusion,  or  whether  we 
must  assume  that  special  excretory  forces  are  at  work  in  the 
lung-tissue.  The  results  of  the  following  experiment  of 
Pflüger  and  his  pupils,  Wolff  berg*  and  Nussbaum,^  are  in 
favor  of  the  former  view.  If  the  giving  off  of  carbonic  acid 
in  the  alveoli  of  the  lungs  simply  follows  the  laws  of  the 
diffusion  of  gases,  we  should  expect  ä  priori  that,  if  a  lobe  of 
the  lung  were  blocked  by  closing  the  corresponding  bronchus, 
the  carbonic  acid  pressure  would  rise  in  the  air-cavities  of  the 
lung  thus  closed  in,  until  it  balanced  the  carbonic  pressure  in 
the  venous  blood  flowing  in,  and  that  then  the  blood  flowing 
out,  i.  e.,  the  arterial  blood  of  the  pulmonary  veins  in  this  same 
lobe,  would  also  have  the  same  COg  tension.  The  experiments 
of  Wolffberg  and  Nussbaum  have  in  fact  shown  that,  under 
these  conditions,  the  pressure  of  CO^  in  the  alveoli  is  the  same 
as  in  the  venous  blood. 

One  pulmonary  lobe  was  successfully  closed  in  the  follow- 
ing manner.  An  elastic  catheter  ^  was  introduced  into  a  branch 
of    one   bronchus   of  a   dog   that   had   been   tracheotomized. 

^  Setschenow,  Sitzungsber.  d.  Wien.  Äkad.,  vol.  xxxvi.  p.  293  :  1859. 
2  Pflüger,  loc.  cit.,  pp.  5,  et  seq. 
^W.  Preyer,  "  Die  Blutkrystalle  "  :  Jena,  1871. 

4  Wolffberg,  Pfliiger's  Arch.,  vol.  iv.  p.  465  :   1871 ;  and  vol.  vi.  p.  23  :  1872. 
'  Nussbaum,  ibid.,  vol.  vii.  p.  296  :  1873. 

^  A  description  and  illustration  of  the  '  lung-catheter '  are  given  by  Wolff- 
berg, ibid.,  vol.  iv.  p.  467,  &c.  :  1871. 


266  LECTURE   XVIII 

The  catheter  had  a  double  wall ;  the  outer,  which  was  made  of 
india-rubber,  was  thinner  towards  the  end  inserted  in  the 
bronchus,  so  that,  when  inflated,  this  end  expanded,  whilst 
the  thicker  portion  of  the  wall  remained  the  same.  This 
flask -like  expansion  of  the  tube  ensured  a  completely  air-tight 
closure  of  the  bronchus.  Ventilation  went  on  unimpeded  in 
the  other  lobes  of  the  same  lung  and  in  the  other  lung,  so  that 
there  could  be  no  retention  of  COg  in  the  blood.  The  pressure 
of  carbonic  acid  was  thus  also  normal  in  the  blood-vessels  of 
the  lobe  that  had  been  stopped  up.  When  the  closure  had 
lasted  long  enough,  a  sample  of  the  gas  could  be  drawn  out 
through  the  inner  tube  of  the  catheter,  and  used  for  analysis. 
The  means  of  numerous  estimates  of  the  enclosed  pulmonary  air 
gave  an  average  pressure  of  COg  of  3.84  per  cent,  of  an  atmos- 
phere, and  of  3.81  per  cent,  for  the  blood  from  the  right 
heart.  The  fact  that  the  latter  figure  is  lower  than  in  the 
above-mentioned  experiments  of  Strassburg,  who  found  a  mean 
of  5.4  per  cent.,  is  explained  by  the  fact  that  the  animals  were 
not  tracheotomized  in  Strassburg's  cases,  and  that,  in  conse- 
quence of  tracheotomy,  the  ventilation  of  the  lung  is  far  more 
complete,  and  the  retention  of  carbonic  acid  in  the  blood  is 
much  less. 

Under  normal  conditions,  if  the  interchange  of  gas  simply 
follows  the  laws  of  difiJusion,  the  pressure  of  CO2  could  never 
be  higher  in  the  alveoli  of  the  lungs  than  in  the  arterial  blood, 
the  two  being  equally  balanced.  If  the  balance  is  complete, 
the  pressure  must  be  the  same ;  if  incomplete,  the  pressure  in 
the  alveoli  must  be  lower,  but  can  never  be  higher.  If  it  were, 
we  should  have  to  assume  that  forces  were  at  work  in  the  lung- 
tissue  to  expel  it.  How  do  the  facts  agree  with  this  deduction  ? 
Strassburg  found  that  the  pressure  of  carbonic  acid  in  the 
arterial  blood  of  the  dog  was  from  2.2  to  3.8  per  cent.,  or  on  an 
average  2.8  per  cent,  of  an  atmosphere.^ 

The  normal  CO2  pressure  in  the  alveoli  cannot  be  ascer- 
tained, but  we  can  determine  its  minimal  value  by  estimating 
the  CO2  pressure  in  the  total  air  expired,  which  is  a  mixture  of 
alveolar  air  and  atmospheric  air.  If  this  minimal  value  should 
prove  higher  than  the  carbonic  acid  pressure  in  the  arterial 
blood,  the  assumption  that  the  interchange  of  gases  proceeds 
only  by  diffusion  would  be  refuted ;  we  should  be  forced  to 
consider  that  there  were  other  special  expelling  forces  at 
work. 

The  amount  of  carbonic  acid  in  the  expired  air  of  the 
dog  has,   so  far  as  I  am   aware,    only    been    estimated    once. 

^  Strassburg,  Pfliiger's  Arch.,  vol.  vi.  p.  77:  1872. 


GASES    OF   THE   BLOOD    AND   RESPIRATION  267 

Wolff  berg  ^  found  from  2.4  to  3.4,  a  mean  of  2.8  per  cent. 
Wolffberg's  dog  was  tracheotomized.  The  COg  tension  in  the 
expired  air  would  be  higher  in  a  dog  breathing  normally,  and 
still  higher  in  the  alveolar  air  than  in  the  expired  air.  These 
experiments  urgently  require  repetition.  These  facts,  so  far,  are 
only  partially  reconcilable  with  the  theory  that  the  interchange 
of  gases  in  the  lungs  proceeds  merely  according  to  the  laws  of 
diffusion. 

The  amount  of  COg  in  the  air  expired  by  human  beings  is 
much  larger:  Vierordt^  found  4.6  per  cent.  COg  in  the  air 
normally  expired,  and  5.2  per  cent,  in  that  expired  after  a  very 
deep  inhalation.  The  pressure  of  carbonic  acid  in  the  arterial 
blood  of  human  beings  is  not  known. 

In  the  short  time  during  which  the  blood  flows  through  the 
capillaries  of  the  lungs,  the  equalization  of  the  difference  in 
tension  is  accomplished  with  a  completeness  which  is  sur- 
prising. This  phenomenon  is  explained  if  the  extent  of  the 
surface  be  considered  over  which  the  interchange  takes  place. 
According  to  an  approximate  valuation  of  the  anatomist 
Huschke,  the  total  inner  surface  of  the  human  lungs  amounts 
to  2000  square  feet,  and  the  whole  of  this  vast  surface  is 
thickly  interwoven  with  a  network  of  capillaries. 

The  experiments  made  to  estimate  the  pressure  of  carbonic 
acid  in  the  tissues  are  attended  with  great  difficulties.  Ä 
priori,  it  must  be  assumed  that  the  greatest  pressure  will  be 
where  the  development  of  carbonic  acid  is  most  considerable : 
therefore  probably  in  the  cells,  in  the  muscular  fibers,  in  all  the 
active  elements — in  fact,  wherever  most  kinetic  energy  is 
liberated.  Now  the  pressure  of  COg  cannot  be  directly 
estimated  in  the  cells  themselves;  an  endeavor  has  there- 
fore been  made  to  estimate  the  partial  pressure  of  this  gas  in 
the  fluids  which  come  most  in  contact  with  the  cells,  i.  e.,  the 
lymph.  It  was  imagined  ä  priori  that  the  lymph,  which  flows 
so  slowly  round  the  cells,  would  be  saturated  far  more  com- 
pletely with  carbonic  acid  than  the  blood,  which  passes  through 
the  capillaries  so  rapidly.  But  as  a  matter  of  fact  this  is  not 
so.  Strassburg  ^  found  the  tension  of  carbonic  acid  invariably 
less  in  the  lymph  than  in  venous  blood.  It  thus  appears  that 
the  stream  of  COg  from  the  cells  into  the  lymph  does  not 
simply  follow  the  laws  of  diffusion.  Why  does  the  bulk  of  it 
diffuse  directly  into  the  blood  ?     The  purpose  is  evident ;  the 

1  Wolfiberg,  Pflüger's  Arch.,  vol.  vi.  p.  478  :  1871. 

2  Vierordt,  "  Physiol,  des  Athmens,"  p.  134  :  Heidelberg,  1845. 

2  Strassburg,  loc.  cit.,  pp.  85-91.  Vide  also  Gaule,  Du  Bois'  Arch.,  pp.  474- 
476  :  1878. 


268  LECTURE   XVIII 

carbonic  acid  reaches  the  lungs  most  rapidly  in  this  manner. 
The  cause,  however,  is  not  yet  known. 

Strassburg  has  also  estimated  the  tension  of  carbonic  acid 
in  dog's  urine,  and  found  it  to  be  about  9  per  cent,  of  an  atmos- 
phere, and  in  the  bile  7  per  cent.  Finally,  he  endeavored 
to  estimate  it  in  the  tissues  of  the  intestinal  wall,  by  injecting 
atmospheric  air  into  a  ligatured  coil  of  intestine  of  a  living 
dog,  and  analyzing  a  sample  of  the  air  after  from  half  an  hour 
to  three  hours ;  he  found  from  7  to  9|  per  cent.  CO2.  From 
these  facts  it  follows  that  the  tension  of  carbonic  acid  is 
greater  in  the  tissues  than  in  the  blood,  which  we  should 
expect  to  be  the  case. 

But  what  would  happen  if  an  animal  were  brought  into  an 
atmosphere  where  the  pressure  of  carbonic  acid  was  already 
as  great  as  in  the  venous  blood  ?  The  interchange  of  gases  in 
the  alveoli  would  be  stopped,  but  only  for  an  instant ;  for  the 
development  of  carbonic  acid  proceeds  unremittingly  in  the 
tissues.  The  amount  of  COg  rises  above  the  normal  both  in 
the  tissues  and  in  the  blood,  and  then  it  will  again  be  given  off 
by  the  walls  of  the  alveoli,  in  consequence  of  the  difference  in 
tension  which  arises. 

But  a  retention  of  carbonic  acid  in  the  blood  and  in  the 
tissues  will  occur  much  sooner,  long  before  the  amount  of  COg 
in  the  inspired  air  is  the  same  as  that  of  the  normal  alveolar 
air.  The  smaller  the  difference  of  the  tension  of  carbonic  acid 
in  venous  blood  and  in  the  alveolar  air,  the  more  slowly  will 
CO2  be  given  off  from  the  blood  to  the  alveolar  air,  and  the 
greater  must  be  the  retention  of  carbonic  acid  in  the  blood  and 
in  the  tissues. 

The  abnormally  high  tension  of  this  gas  in  the  tissues  is 
the  cause  of  disturbances,  especially  in  certain  parts  of  the 
central  nervous  system.  The  increasing  partial  pressure  of  the 
carbonic  acid  acts  above  all  on  the  respiratory  center,  causing 
deeper  respiration.  If  the  retention  of  carbonic  acid  be  so 
great  that  the  deeper  respiration  cannot  overcome  it,  it  acts  also 
on  other  parts  of  the  central  nervous  system,  and  the  animals 
finally  die  with  symptoms  of  narcosis. 

If  animals  be  placed  in  an  air-tight  compartment,  and  be 
made  to  breathe  an  artificial  mixture  of  air  rich  in  oxygen,  they 
die  of  carbonic  acid  poisoning  long  before  the  partial  pressure 
of  the  oxygen  has  sunk  to  normal.^ 

^  Müller,  Sitzungsber.  d.  Akad.  d.  Wissensch.  zu  Wien.,  Math.  Nat.  Classe, 
vol.  xxxiii.  p.  1.36,  et  seq. :  1859;  P.  Bert,  "La  pression  barometrique,"  p.  983  : 
Paris,  1878 ;  Friedländer  and  Herter,  Zeitschr.  /.  physiol.  Chem.,  vol.  ii.  p.  99  : 

1878. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  269 

If  the  volumes  of  the  inspired  and  expired  air  in  normal  res- 
piration be  compared,  the  latter  is  always  found  to  be  larger. 
The  explanation  is  to  be  sought  in  the  fact  that  the  air  has  be- 
come warmer  in  the  lung  and,  owing  to  the  temperature  of  the 
body,  has  been  almost  saturated  with  aqueous  vapor.  The  quan- 
tity of  water  which  leaves  the  body  in  this  way  during  the  course 
of  a  day  amounts  to  from  400  to  800  grms.  It  varies  with  the 
dryness  of  the  inspired  air. 

But  if,  on  the  other  hand,  the  volumes  of  the  inspired  and 
expired  air  be  compared  after  desiccation,  and  reduced  to  the 
same  temperature  and  pressure,  the  volume  of  expired  air  is 
usually  somewhat  smaller.  This  is  readily  explained  if  we 
consider  that,  in  the  combustion  of  food-stuffs,  it  is  only  the  car- 
bohydrates which  produce  a  volume  of  carbonic  acid  equal  to 
that  of  the  oxygen  used  up,  the  proteids  and  fats  yielding  a 
smaller  one. 

The  carbohydrates  are  known  to  contain  exactly  so  much 
oxygen  as  is  requisite  for  the  saturation  of  the  hydrogen.  If 
therefore  the  entire  molecule  becomes  oxidized  to  carbonic  acid 
and  water,  exactly  two  oxygen  atoms  must  be  taken  up  to  every 
carbon  atom.  Two  atoms  (that  is,  one  molecule  of  oxygen) 
form  with  one  atom  of  carbon  one  molecule  of  carbonic  acid. 
Now,  it  is  well  known  that  an  equal  number  of  molecules  oc- 
cupies an  equal  volume.  Consequently,  the  volumes  of  COj 
formed  during  the  combustion  of  the  carbohydrates  must  be 
equal  to  the  volume  of  oxygen  used  up. 

The  fats,  on  the  other  hand,  contain  fewer  oxygen  atoms 
than  are  necessary  for  the  saturation  of  the  hydrogen  atoms  :  in 
stearic  acids  (CjgHggOg),  only  four  of  the  thirty-six  hydrogen 
atoms  can  be  saturated  by  the  oxygen  present ;  sixteen  more 
atoms  of  the  inspired  oxygen  must  be  used  up  in  order  to  com- 
plete the  combustion  of  the  hydrogen,  and  these  do  not  reappear 
in  the  expired  air.  Glycerin  (CgHgOg)  also  contains  two  atoms 
more  hydrogen  than  are  saturated  by  the  oxygen  present.  Thus, 
for  the  complete  combustion  of  the  fats,  far  more  oxygen  must 
be  taken  up  than  is  requisite  for  the  combustion  of  their  carbon ; 
and  for  this  reason  all  the  inspired  oxygen  does  not  reappear  in 
the  expired  carbonic  acid. 

This  is  also  the  case  with  the  proteids.  One  hundred  grms. 
of  proteid  contain  7  grms.  of  hydrogen.  In  order  to  reduce 
these  to  water  by  combustion,  7  x  8  =  56  grms.  of  oxygen  are 
necessary.  But  100  grms.  of  proteid  matter  contain  at  most 
24  grms.  of  oxygen.  Extra  oxygen  must  therefore  be  inspired 
for  the  purpose  of  oxidizing  the  hydrogen,  besides  the  amount 
necessary  for  the  oxidation  of  the  carbon.     Only  the  estimate 


270  LECTURE   XVIII 

is  rendered  more  complicated  with  proteid,  because  hydrogen 
and  oxygen  atoms  are  also  eliminated  in  the  nitrogenous  waste 
products,  and  because  oxygen  is  also  used  up  in  oxidizing  the 
sulphur. 

The  proportion  of  the  expired  volimie  of  carbonic  acid 
to  the  inspired  volume  of  oxygen  is  termed  the  respiratory 
quotient. 

The  carbohydrates  preponderate  in  the  diet  of  herbivora. 
The  respiratory  quotient  in  these  cases  is  nearly  equal  to  1. 
With  Carnivora,  on  the  other  hand,  where  the  food  is  poor  in 
carbohydrates  and  rich  in  proteids  and  fats,  the  respiratory 
quotient  must  be  considerably  less  than  1.  It  is  usually  found 
to  be  about  |. 

The  respiratory  quotient  estimated  from  the  constituents  of 
food  only  agrees  with  that  actually  found  ^  if  the  estimation  of 
the  respiratory  gases  be  carried  out  for  some  time,  if  possible 
for  twenty-four  hours.  In  short  spaces  of  time,  the  propor- 
tion may  be  very  materially  altered,  because  the  taking  in  of 
oxygen  and  the  giving  out  of  carbonic  acid  do  not  occur  simul- 
taneously. A  considerable  part  of  the  carbon  may  be  split 
off  from  the  carbohydrates  as  carbonic  acid  without  any  oxy- 
gen being  taken  in,  as  we  see  in  alcoholic  and  butyric  acid 
fermentation ;  the  by-products  then  formed,  which  are  poor  in 
oxygen,  are  oxidized  later,  after  the  COg  previously  given  off 
has  been  expired.  In  this  way  it  may  happen  that  the  expired 
volume  of  COg  may  for  a  time  be  larger  than  the  inspired 
oxygen  volume,  and  the  respiratory  quotient  may  be  greater 
than  1. 

In  herbivora,  it  sometimes  happens  that  the  whole  volume 
of  COg  expired  in  twenty-four  hours  is  larger  than  the  volume 
of  inspired  oxygen.     The  following  statement  will  explain  this. 

^  A  description  and  illustration  of  the  apparatus  used  for  the  quantitative 
estimate  of  the  interchange  of  gases  during  longer  periods,  and  especially  of  Reg- 
nault's,  Reiset's,  and  Pettenlcofer's  respiratory  apparatus,  are  to  be  found  in  every 
text-book  of  physiology.  Any  one  desirous  of  reading  the  original  description 
by  the  authors,  is  referred  to  the  celebrated  work  of  Regnault  and  Reiset  in  the 
Ann.  de  Ohim.  et  de  Phys.^  vol.  xxvi.:  1849 ;  also  under  the  separate  title,  "  Re- 
cherches  chimiques  sur  la  respiration  des  animaux  des  diverses  classes  "  :  Bach- 
ellier,  1849  ;  translated  in  Liebig's  Ann.  d.  Chem.  u.  Pharm.,  vol.  Ixxiii.  pp.92, 
129,  257  :  1850.  The  description  of  Pettenkofer's  respiratory  apparatus  is  to  be 
found  in  Liebig's  ^nw.  de  Chem.  u.  Pharm.,  vol.  ii.  p.  1,  Suppl.:  1862.  This  ap- 
paratus was  specially  constructed  for  experiments  on  human  beings.  Voit  modi- 
fied it  somewhat  for  smaller  animals.  The  exact  illustration  and  description  are 
given  in  Zeitschr.f.  Biolog.,  vol.  xi.  p.  541  :  1875.  A  modification  of  Regnault's 
and  Reiset's  apparatus  for  examining  the  respiration  of  aquatic  animals  was  de- 
scribed by  Jolyet  and  Regnard  in  Arch,  de  physiol.  normale  et  patholog.,  ser.  ii. 
vol.  iv.  p.  44  :  1877.  More  recently  Hoppe-Seyler  has  constructed  a  respiratory 
apparatus  on  Regnault's  principle  for  experiments  on  man.  Zeitschr.  f.  physiol. 
Chem.,  vol.  xix.  p.  574  :  1894. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  271 

"Vegetable  food  contains  organic  acids,  which  are  richer  in 
oxygen  than  the  carbohydrates,  and  for  this  reason  they  use  up, 
during  their  conversion  into  carbonic  acid  and  water,  a  smaller 
volume  of  oxygen  than  that  corresponding  to  the  volume  of 
carbonic  acid  formed.  Tartaric  acid  with  2^  vols,  of  oxygen 
gives  4  vols,  of  CO^ :  CJip,  -f  50  =  4CÖ^  +  3Hp.  But 
carbonic  acid  may  be  developed  from  another  source  without 
oxygen  being  taken  up.  The  carbohydrates  may  undergo 
marsh-gas  fermentation  in  the  intestine  :  CgH^jOg  =  SCOg  + 
3CH,.  The  carbonic  acid  is  absorbed  from  the  intestine  and 
breathed  out  from  the  lungs,  but  the  marsh-gas  remains  unoxi- 
dized  (pp.  279,  280). 

It  is  important  to  know  all  these  conditions  upon  which  the 
respiratory  quotient  depends.  In  the  experiments  on  meta- 
bolism, the  size  of  this  quotient  affords  many  indications 
from  which  the  chemical  processes  in  the  tissues  may  be 
judged. 

In  speaking  of  respiration,  we  have  hitherto  meant  only  the 
respiration  through  the  lungs.  The  question  now  remains  for 
us  to  consider  whether  there  is,  in  human  beings,  such  a  thing 
as  CUTANEOUS  RESPIRATION.  It  Undoubtedly  exists  among  the 
lower  animals,  as  well  as  among  certain  of  the  lower  vertebrata. 
Among  the  amphibia,  the  interchange  of  gases  goes  on  more 
extensively  by  means  of  the  skin  than  by  the  lungs.  This  was 
known  even  to  Spallanzani.^  He  proved  that  many  kinds  of 
amphibia  lived  longer  after  extirpation  of  the  lungs  than  after 
their  skins  were  varnished  over.  There  is  however  this  objec- 
tion to  the  above  experiment,  i.  e.,  that  the  varnishing  of  the 
skin  would  be  prejudicial  in  other  ways.  Spallanzani's  experi- 
ments have  therefore  been  repeated  with  many  alterations.' 
Fubini  estimated  the  whole  of  the  COg  given  out  by  normal 
frogs  and,  on  comparing  it  with  that  given  out  by  frogs  with 
their  lungs  extirpated,  found  that  the  latter  amount  was  only 
a  little  less.  To  this  experiment  the  objection  may  also  be 
raised  that  after  extirpation  of  the  lungs  the  output  of  COg  by 
the  skin  was  no  longer  normal,  but  increased  by  vicarious 
activity.  Ferd.  Klug  therefore  constructed  a  special  apparatus, 
in  which  the  head  and  body  were  each  in  separate  compart- 
ments. The  separation  was  effected  by  means  of  a  sheet  of 
india-rubber,  through  which  the  head  was  passed.     The  result 

^  Spallanzani,  "Memoires  sur  la  respiration,  traduits  par  Senebier,"  p.  73  : 
Geneve,  1803. 

2  Vide  Fubini,  Moleschott's  Unt.  z.  Naturlehre,  vol.  xii.  p.  100  :  1878  ;  and 
Ferd.  Klug,  DuBois'  Arch.,  p.  183  :  1884,  containing  also  a  critical  notice  of  the 
earlier  literature. 


272  LECTTJEE   XVIII 

of  this  experiment  was  found  to  be  that  only  a  very  small  part 
of  the  CO2  was  given  out  through  the  lungs. 

The  most  exact  estimates  on  the  output  of  COg  through  the 
skin  of  human  beings  were  made  by  H.  Aubert.^  The  person 
experimented  on  sat  naked  in  an  air-tight  box,  the  top  of  which 
was  made  of  india-rubber.  The  head  came  out  of  a  round  hole 
in  this  covering,  which  fitted  tightly  round  the  neck,  so  that  no 
air  could  get  in.  A  stream  of  air  was  now  admitted  into  the 
enclosed  space.  The  air  had  been  previously  freed  from  all 
carbonic  acid,  and  on  coming  out  was  passed  through  flasks 
containing  baryta  water.  The  experiment  lasted  for  two  hours. 
From  the  carbonic  acid  absorbed  during  this  time  by  the 
solution  of  baryta,  the  quantity  eliminated  in  twenty-four  hours 
was  estimated.  Seven  experiments  showed  that  in  twenty-four 
hours  a  man  gives  out  by  the  skin  a  maximum  of  6.3  grms.,  a 
minimum  of  2.3,  or  an  average  of  3.9   grms.  of  carbonic  acid. 

This  amount  of  COg  is  exceedingly  small  in  comparison  with 
that  proceeding  from  the  lungs,  which  in  human  beings  amounts 
to  from  800  to  1200  grms.  in  twenty-four  hours.  It  is  even 
doubtful  whether  the  small  quantity  of  COj  found  was  really 
given  off  by  the  skin  in  the  form  of  gas.  It  is  possible  that  it 
arose  from  the  decomposition  of  the  secretions  of  the  skin  and 
of  the  cast-off  epidermis.  Still  more  dubious  are  the  state- 
ments that  small  quantities  of  oxygen  are  taken  up  through 
the  human  skin. 

Until  quite  recently,  it  was  believed  that  not  only  is 
carbonic  acid  given  out  through  the  skin,  but  also  certain 
gaseous  organic  compounds  of  a  more  complex  nature.  This 
has  been  the  explanation  offered  for  the  injurious  effects  of  a 
great  many  people  being  shut  up  together  in  a  small  room.  It 
was  thought  that  these  organic  vapors  have  a  very  low  tension  ; 
that  the  air  soon  reaches  saturation  as  far  as  they  are  concerned, 
and  cannot  receive  any  more  of  them  from  the  organism,  unless 
it  be  rapidly  changed  and  renewed.  If  these  vapors,  in  how- 
ever small  a  quantity,  remain  behind  and  collect  in  the  body, 
they  act  on  certain  parts  of  the  nervous  system,  and  through 
these  on  the  whole  metabolism,  just  as  they  do  on  our  olfactory 
nerves  after  they  have  passed  into  the  air,  when  they  may  even 
cause  vomiting.^ 

This  idea  of  the  injurious  effects  arising  from  the  suppressed 
action  of  the  skin  is  as  old  as  the  history  of  medicine,  and  even 
up  to  the  present  time  the  perspirabile  retentum  plays  an  im- 
portant part  in  the  etiology  of  certain  diseases.     This  idea  in- 

^  H.  Aubert,  Pfliiger's  Arch.,  vol.  vi.  p.  539  :  1872. 

2  Pettenkofer,  Liebig's  Ann.  d.   Chem.  u.  Pharm.,  vol.  ii.  Suppl.  p.  5  :  1862. 


GASES    OF    THE    BLOOD    AND    EESPIEATION  273 

duced  Pettenkofer,  in  his  researches  on  respiration,  to  abandon 
the  method  of  Regnault  and  Reiset,  and  to  construct  a  new 
respiratory  apparatus,  in  which  a  constant  current  of  fresh  air 
passed  through  the  compartment  that  held  the  person  or  ani- 
mal. Pettenkofer  had  found  that  when  the  proportion  of  COg 
had  risen  to  0.1  per  cent,  in  a  room  filled  with  people,  the  air 
began  to  smell,  and  that  when  it  rose  to  1  per  cent,  the  air 
became  almost  unendurable.  But  if  he  developed  carbonic 
acid  in  a  room,  by  acting  on  bicarbonate  of  sodium  with  sul- 
phuric acid  until  the  COg  in  the  air  amounted  to  1  per  cent., 
he  found  that  he  could  remain  in  this  room  quite  comfortably 
for  a  considerable  time.  It  is  therefore  not  the  carbonic  acid 
itself  that  is  the  harmful  product  in  so-called  bad  air;  but, 
according  to  Pettenkofer,  the  CO2  is  a  measure  of  the  injurious 
products  of  perspiration  which  are  as  yet  unknown  to  us. 

All  endeavors  to  discover  what  these  harmful  products  of 
perspiration  are  have  hitherto  failed.  The  latest  experiments 
were  made  by  Hermans^  in  the  Institute  of  Hygiene  in 
Amsterdam.  A  man  was  shut  in  an  air-tight  case  of  sheet- 
iron.  The  first  signs  of  dyspnea  appeared  when  the  COg  in 
the  air  rose  above  3  per  cent.  If  the  carbonic  acid  was  re- 
moved by  absorption,  no  inconvenience  was  experienced,  even 
when  the  amount  of  oxygen  in  the  box  sank  to  10  per  cent. 
In  order  to  discover  the  supposed  organic  products  of  perspira- 
tion, air  was  first  passed  through  the  case,  and  then  through  an 
absorption  apparatus.  When  passed  through  titrated  sulphuric 
acid,  the  titre  was  always  found  to  be  unaltered.  If  the  air 
was  passed  over  red-hot  oxid  of  copper,  the  amount  of  CO2 
and  of  water  did  not  increase.  In  the  same  way  the  titre  of  a 
boiling  acid  or  alkaline  permanganate  solution  was  found  to  be 
unchanged,  even  after  many  liters  of  the  air  taken  from  the 
case  towards  the  end  of  the  experiment  had  been  slowly  passed 
through  it.  Neither  did  the  condensed  water,  obtained  from 
the  issuing  air  after  being  cooled  by  ice,  nor  the  condensed 
water  from  the  sides  of  the  case,  alter  the  titre  of  boiling  per- 
manganate solution.  There  was  likewise  no  disagreeable  smell. 
The  greatest  care  had  been  taken  to  see  that  the  clothing  and 
person  of  the  man  experimented  upon  were  perfectly  clean. 
Hermans  therefore  comes  to  the  conclusion  that  when  healthy 
people  give  out  malodorous  substances  in  the  atmosphere,  these 
come,  not  from  normal  perspiration,  but  from  the  processes  of 
decomposition  caused  by  the  dirty  state  of  the  body  or  clothes. 

The  medical  men  who  believe  in  the  harmfulness  of  the 
perspirabile  retentum,  ground  their  belief  on  the  following  facts : 

1  Hermans,  Arch.  f.  Hygiene,  vol.  i.  p.  5  :  1883. 
18 


274  LECTURE    XVIII 

(1)  The  injurious  effect  on  animals  whose  skin  has  been  ren- 
dered impervious  to  perspiration  by  varnishing ;  and  (2)  the 
fatal  effect  of  extensive  burns  of  the  skin.  But  these  facts 
must  be  differently  interpreted. 

The  death  of  varnished  animals  may  be  explained  by  an  in- 
creased loss  of  heat.^  In  the  first  place,  the  animals  in  all  such 
experiments  were  shaved  before  being  varnished,  thus  being 
deprived  of  their  natural  protection  ;  in  the  second  place,  the 
varnishing  appears  to  damage  the  vasomotor  nerves ;  the 
cutaneous  vessels  become  dilated,  the  surface  of  the  body 
becomes  warmer  than  it  normally  is,  and  the  loss  of  heat  is 
greater.  In  consequence  of  this,  the  temperature  of  the  body 
sinks,-  and  the  animals  die  of  cold.  If  an  animal  be  only 
partially  varnished,  it  is  found  that  the  varnished  parts  are 
warmer  than  the  rest  of  the  skin.  A  varnished  animal  gives 
out  more  heat  in  the  calorimeter  than  a  normal  one  does.  If 
the  cooling  be  prevented  by  wrapping  the  varnished  animal  in 
wool,  or  by  placing  it  in  a  warm  place,  it  remains  alive  and 
does  not  become  ill.  Besides,  only  those  animals  fall  ill  on 
being  varnished  that  have  a  delicate  skin,  and  a  surface  that  is 
large  in  proportion  to  their  small  weight,  as  for  instance  rabbits. 
Larger  animals  with  a  tough  skin,  such  as  dogs,  remain  per- 
fectly well  with  their  whole  body  varnished  over. 

Senator,^  in  Berlin,  even  ventured  to  varnish  human  beings. 
He  had  two  patients  suffering  from  rheumatism,  which  is  often 
thought  to  be  caused  by  the  arrest  of  the  action  of  the  skin. 
Any  interference  with  this  action  should  therefore  be  attended 
with  dire  consequences.  The  extremities  of  these  patients 
were  encased  in  sticking-plaster,  and  almost  the  whole  trunk 
was  thickly  painted  with  collodion,  mixed  with  a  little  castor 
oil  to  make  it  less  brittle.  Only  the  skin  of  the  head,  neck, 
buttock,  and  genitals  remained  free.  One  patient  twice  re- 
mained in  this  condition  for  twenty-four  hours,  the  other  for 
fully  eight  days  !  The  third  experiment  was  made  on  a  female 
patient  with  chronic  pemphigus.  The  whole  body,  and  even 
the  face,  was  thickly  covered  with  common  tar,  and  the  head, 
which  had   been    shaven,  with  oleum    rusci.^     This   air-tight 

'  Laschkewitsch,  Arch.  f.  Anat.  u.  Physiol.,  p.  61 :  1868 ;  K.  Winternitz, 
Arch.  J.  exper.  Path.  u.  Pharm.,  vol.  xxxiii.  p.  286:  1894. 

^»Senator,  Virchow's  Arch.,  vol.  Ixx.  p.  182  :  1877. 

'  [Oleum  rusci  sive  pix  betulimum  sive  oleum  betulse  empyreumaticum,  is  a 
tarry  product  obtained  from  all  parts  of  the  birch  tree,  and  in  great  favor  as  a 
popular  remedy  for  all  kinds  of  diseases  in  Poland  and  Russia.  It  is  also  em- 
ployed in  the  fabrication  of  certain  liqueurs,  and  especially  in  the  preparation  of 
Russian  leather,  to  which  it  imparts  its  characteristic  odor  (see  Dr.  Hager's 
"Handbuch  der  pharmaceutischen  Praxis":  Berlin,  1880;  and  the  United 
States  Dispensary :  1883).] 


GASES    OF    THE    BLOOD    AND    RESPIEATION  275 

covering  was  not  removed  for  ten  days,  but  no  injurious  conse- 
quences occurred  in  any  of  the  three  cases. 

Finally,  as  regards  the  fatal  effect  of  extensive  burns  on  the 
skin,  there  may  be  other  explanations  than  that  of  the  perspira- 
bile  retentum;  in  fact,  in  recent  times  many  others  have  been 
attempted.  We  know  that  even  a  moderate  rise  of  temperature 
will  alter  and  destroy  the  blood-corpuscles.^  This  led  to  the 
supposition  that  the  blood-cells  which  pass  through  the  capil- 
laries of  the  skin  during  a  burn  become  destroyed  by  the  higher 
temperature,  and  that  their  decomposition-products  indirectly 
cause  the  symptoms  which  ensue.  And  in  fact  a  constituent  of 
the  corpuscles,  the  hemoglobin,  was  found  in  the  plasma  of  the 
blood  after  a  burn,  and  the  hemoglobin,  or  a  derivative,  was 
found  in  the  urine.^  According  to  Hoppe-Seyler's  ^  and  Tap- 
peiner's  *  investigations,  however,  the  amount  of  hemoglobin  in 
the  blood-plasma  after  burns  is  very  slight,  and  was  even  en- 
tirely absent  in  one  case  which  ended  fatally.  Neither  it  nor 
its  derivatives  invariably  occur  in  the  urine.  On  the  other 
hand,  the  following  fact  observed  by  Tappeiner  is  very  inter- 
esting :  he  found  the  blood  of  patients  with  extensive  skin-burns 
to  be  much  richer  in  corpuscles  and  poorer  in  plasma  than  nor- 
mal blood.  This  thickening  of  the  blood  is  accounted  for  by 
the  transudation  of  lymph  at  the  burnt  places,  and  is  perhaps 
the  primary  cause  of  all  the  symptoms  and  of  death. 

We  thus  see  that  there  is  no  real  ground  for  assuming  that 
any  gaseous  products  are  excreted  by  the  human  skin.  Our 
knowledge  of  the  chemistry  of  cutaneous  activity  is  altogether 
very  limited.  Nothing  certain  is  known  concerning  the  chemical 
composition  of  perspiration,'  and  there  is  at  present  no  reason 
for  considering  this  secretion  to  have  any  other  use  than  that 
of  the  purely  physical  action  in  regulating  the  temperature  of 
the  body.  The  evaporation  of  water  on  the  surface  of  the  body 
is  the  most  effectual  means  of  cooling  it.  It  must  not  be  for- 
gotten what  an  enormous  amount  of  heat  becomes  latent  when 

1  Max  Schultze,  Arch.  f.  mik.  Anat.,  vol.  i.  p.  26 :  1865. 

^  Wertheim,  Wiener  med.  Presse,  No.  13 :  1868 ;  Ponfick,  Berl.  klin.  Wo- 
chenschr.,  No.  46:  1877;  Centralbl.f.  d.  med.  Wissensch.,  Nos.  11,  16:  1880;  von 
Lesser,  Virchow's  Arch.,  vol.  Ixxix.  p.  248 :  1880. 

*  Hoppe-Seyler,  Zeitschr.  f.  phyaiol.  Chem.,  vol.  v.  pp.  1,  344:  1881. 

■*  Tappeiner,  Centralbl.  f.  d.  med.  Wissensch.,  vol.  xix.  pp.  385,  401:  1881. 

^  Vide  0.  Funke,  Moleschott's  Unter,  z.  Naturlehre  d.  ßlenschen  u.  der 
Thiere,  vol.  iv.  p.  36 :  1858  ;  and  W.  Leube,  "  Ueber  den  Antagonismus  zwischen 
Harn-  und  Schweissecretion  und  dessen  therapeutische  Bedeutung,"  Deutsch. 
Arch.  f.  klin.  Med.,  vol.  vii.  p.  1 :  1870.  An  account  of  the  previous  literature 
is  also  given.  Compare  also  A.  Kast,  "Ueb.  aromatische  Fäulnissprodukte  im 
menschlichen  Schweisse,"  Zeitschr.  f.  physiol.  Chem.,  vol.  xi.  p.  501 :  1887.  P. 
Argutinsky,  Pflüger's  Arch.,  vol.  xlvi.  p.  594:  1890;  E.  Cramer,  Arch.  f.  Hy- 
giene, vol.  X.  p.  231 :  1890. 


276  LECTUEE    XVIII 

water  passes  from  the  liquid  to  the  gaseous  state.  The  secre- 
tion of  perspiration  is  entirely  absent  in  many  animals,  as  in 
the  dog,  and  is  replaced  by  a  more  copious  evaporation  from  the 
surface  of  the  lungs. 

Before  concluding  the  chapter  on  respiration  and  the  behavior 
of  gases  in  the  body,  we  must  consider  the  gases  which  occur  in 
the  alimentary  canal,  their  origin,  and  their  behavior  under 
physiological  and  pathological  conditions. 

The  GASES  in  the  alimentary  canal  arise  from  four 
sources :  (1)  Atmospheric  air  is  continually  being  swallowed 
with  the  saliva,  with  food  and  drink ;  part  of  it  escapes  again  by 
the  esophagus,  but  the  rest  passes  into  the  intestine ;  (2)  gases 
arise  by  fermentative  processes  in  the  contents  of  the  stomach 
and  intestine ;  (3)  gases  diffuse  from  the  tissues  of  the  intes- 
tinal wall  into  the  intestine ;  and  (4)  CO2  is  liberated  when  the 
sodium  carbonate  of  the  intestinal  juice  is  neutralized. 

The  following  gases  have,  up  to  the  present,  been  detected 
in  the  alimentary  canal  of  human  beings  and  of  mammals  :  ^ 
O,  N,  CO,,  H,  CH„  H,S. 

Oxygen  reaches  the  alimentary  canal  only  by  the  air  that  is 
swallowed,  and  disappears  almost  entirely  in  the  stomach,  partly 
by  uniting  with  the  reducing  substances  which  proceed  from  the 
fermentative  processes  already  set  up  in  the  stomach,  and  espe- 
cially with  the  nascent  hydrogen  arising  from  butyric  acid  fer- 
mentation, and  partly  by  diffusion  into  the  tissues  of  the  gastric 
wall.  Traces  of  oxygen  could  still  be  found  in  the  gases 
obtained  from  the  upper  portion  of  the  intestine,  but  none  in 
that  from  the  lower  parts.  Planer  injected  atmospheric  air  into 
a  ligatured  small  intestine  of  a  living  dog,  and  even  after  one 
and  a  half  hours,  half  of  the  oxygen  had  disappeared  from  the 
air  and  had  been  replaced  by  carbonic  acid.  In  the  case  of  a 
few  fish,  the  diffusion  of  the  atmospheric  oxygen  swallowed  by 
them  through  the  walls  of  the  alimentary  canal,  plays  an  impor- 
tant part  in  the  process  of  respiration.^ 

Nitrogen  also  reaches  the  alimentary  canal  with  the  air 
swallowed,  but  does  not  diffuse  into  the  tissues  of  the  intestinal 
wall,  because  the  partial  pressure  of  the  nitrogen  is  very  nearly 
the  same  in  this  latter  as  in  atmospheric  air.     It  must,  on  the 

^Planer,  Sitzungsber.  d.  k.  Akad.  d.  W.  zu  Wien.,  vol.  xlii.  p.  307:  1860;  E. 
Ruge,  ibid.,  vol.  xliv.  p.  739  :  1862  ;  C.  B.  Hofmann,  Wiener  med.  Wochenschr., 
1872 ;  Tappeiner,  Zeitschr.  f.  physiol.  Chem.,  vol.  vi.  p.  432 :  1882  ;  Zeitschr.  f. 
Biolog.,  vol.  xix.  p.  228  :  1883;  and  vol.  xx.  p.  52:  1884;  Arbeit,  a.  d.  pathol. 
Inst.  z.  München.,  edit,  by  Bollinger,  pp.  215,  226  :  Stuttgart,  1886. 

2Erman,  Ann.  d.  Physik,  vol.  xxx.  p.  113  :  1808  ;  Leydig,  Arch.  f.  Anat.  u. 
Physiol.,  p.  3  :  1853 ;  Baumert,  "  Chemische  Untersuchung  über  die  Respiration 
des  Schlammpeitzgers  "  :  Breslau,  1855. 


GASES    OF    THE    BLOOD    AND    RESPIRATION  277 

contrary,  be  assumed  that  nitrogen  diffuses  out  of  the  tissues  of 
the  intestinal  wall  into  the  intestine.  This  occurs  in  the  lower 
portion  of  the  intestine,  in  proportion  as  other  gases  are  de- 
veloped by  fermentation  and  the  partial  pressure  of  the  nitrogen 
sinks.  The  intestinal  gases  as  a  matter  of  fact  always  contain 
an  abundance  of  nitrogen. 

Hydrogen  is  formed  in  large  quantities  by  fermentative 
processes,  and  especially,  together  with  COg,  in  butyric  acid 
fermentation.  This  latter  form  of  fermentation  can  always 
be  detected  in  the  contents  of  the  large  and  small  intestine.^ 
As  already  mentioned,  marsh-gas  arises,  with  carbonic  acid, 
by  the  decomposition  of  cellulose.  But  these  are  not  the  only 
two  processes  of  fermentation  by  which  CO2,  H,  and  CH^ 
are  formed  in  the  intestine.  Ruge  found  marsh-gas  in  the 
gases  of  the  colon  of  living  people,  even  after  a  diet  exclusively 
composed  of  meat ;  and  Tappeiner  found  abundance  of  marsh- 
gas  and  hydrogen  in  the  gases  of  pigs'  colons,  after  they  had  been 
fed  for  three  weeks  entirely  on  meat.  These  gases  proceed 
not  only  from  the  decomposition  of  carbohydrates,  but  also  of 
proteids.  KunkeP  found  that  the  gases  produced  by  artificial 
pancreatic  digestion,  without  excluding  the  fermentative  organ- 
isms, contained  as  much  as  60  per  cent.  H,  and  1.6  per  cent, 
marsh-gas ;  and  Tappeiner  ^  showed  that  sterilized  solutions  of 
common  salt  with  peptone  and  fibrin,  when  mixed  with  a  little 
of  the  intestinal  contents,  developed  a  mixture  of  gases  which 
contained  as  much  as  40  per  cent.  H,  and  as  much  as  19  per 
cent.  CH^.  It  is  noteworthy  that  in  one  of  these  experiments 
Tappeiner  produced  from  a  solution  of  peptone  a  mixture  of 
gases  which  contained  99.65  per  cent.  CO2,  as  well  as  0.14  H 
and  0.21  CH^.  In  the  intestine  fermentations  appear  to  go 
on  in  which  carbonic  acid  alone,  without  any  other  gas,  is 
developed  from  proteid. 

Besides  this,  carbonic  acid  is  developed  in  large  quantity 
through  the  neutralization  of  the  acid  chyme  by  the  sodium 
carbonate  of  the  intestinal  juice.  If  we  may  assume  for 
human  beings  the  same  proportion  of  hydrochloric  acid  in  the 
gastric  juice  which  was  found  by  Carl  Schmidt  in  the  dog,  it 
would  appear  that  6  liters  of  CO2  are  daily  liberated  in  our 
intestine  by  neutralization  of  the  hydrochloric  acid.  We  have 
to  add  the  still  larger  quantity  set  free  by  the  neutraliza- 
tion of  lactic  and  butyric  acids,  which  are  constantly  formed 

^  Compare  Eubuer,  Zeitsclir.  f.  Biolog.,  vol.  xix.  p.  84,  et  seq. ;  1883. 
2  Kunkel,  Verhandl.  d.  physik.-med.  Gesellsch.  in  Wurzburg,  N.  F.,  vol.  viii. 
p.  134 :  1874. 

^  Tappeiner,  Ärb.  a.  d.  patholog.  Inst,  in  München,  vol.  i.  p.  218  :  1886. 


278 


LECTURE    XVIII 


in  the  intestine  from  the  carbohydrates  of  food.  Still,  we  are 
not  inconvenienced  by  these  large  volumes  of  COg,  for  the  co- 
efficient of  absorption  of  carbonic  acid  is  very  high,  and  the 
partial  pressure  of  COg  in  the  intestinal  walls  is  scarcely  ever 
higher  than  10  per  cent,  of  an  atmosphere.  Therefore,  as 
soon  as  the  bowel  contains  more  than  10  per  cent,  of  COg, 
diffusion  into  the  blood  must  commence.  The  proportion  of 
carbonic  acid  in  intestinal  gases  is  commonly  from  20  to  50 
per  cent.,  and  more.  It  follows  that  there  is  constantly  an 
active  current  of  carbonic  acid  from  the  intestine  into  the 
blood.  In  the  experiments  on  dogs  with  duodenal  fistulae, 
Mering  has  shown  that  the  absorption  of  COg  begins  even  in 
the  stomach.  The  COg  developed  in  the  bowel  is  exhaled  by 
the  lung. 

On  the  other  hand,  hydrogen  may  give  rise  to  much  dis- 
comfort, owing  to  its  very  low  coefficient  of  absorption.  It 
follows  that  patients  suffering  from  chronic  dyspepsia  and 
disposed  to  flatulence,  must  be  extremely  careful  to  avoid  such 
articles  of  diet  as  tend  to  a  butyric  fermentation.  According 
to  the  observations  of  Huge  and  Tappeiner,  milk  appears  to  be 
especially  injurious  in  this  respect.  The  experience  of  many 
patients  coincides  with  this  view.  In  the  same  way  starchy 
foods,  which  are  hard  to  digest,  are  to  be  avoided,  because  they 
convey  large  quantities  of  carbohydrates  into  the  lower  portion 
of  the  small  intestine,  the  alkalinity  of  which  encourages 
butyric  fermentation.  It  would  be  wise  to  administer  carbo- 
hydrates in  the  form  of  stewed  fruits,  because  we  thus  convey 
with  them  acids  into  the  bowels  and  because  the  acids  prevent 
butyric  fermentation.  There  are  many  patients  with  whom 
cereals,  the  leguminosse,  and  potatoes  disagree,  but  who  are 
able  to  take  stewed  fruits  with  rice,  which  is  easily  digested 
and  which  is  manifestly  almost  entirely  absorbed  in  the  upper 
part  of  the  bowel. 

The  following  table  gives  the  coefficients  of  absorption  of 
the  intestinal  gases.  They  have  been  determined  by  Bunsen 
at  a  temperature  of  15°  C.  It  is  to  be  regretted  that  they 
have  not  also  been  determined  for  the  body-temperature. 


Nitrogen 0.01478 

Hydrogen 0.01930 

Oxygen 0.02989 


CH^ 0.03909 

CO, 1.0020 

H,S 3.2326 


The  amount  of  sulphuretted  hydrogen  contained  in  the  intes- 
tinal gases  is  very  small,  and  cannot  be  quantitatively  deter- 
mined. It  is  however  conceivable  that  the  amount  developed 
in    the  bowel    is    sometimes    larger  than    might   be  supposed 


GASES   OF   THE   BLOOD    AND    RESPIEATION  279 

from  the  small  amount  contained  in  the  intestinal  gases.  We 
must  not  forget  how  high  the  coefficient  of  absorption  of  sul- 
phuretted hydrogen  is,  being  one  hundred  times  higher  than 
that  of  oxygen  which  is  so  easily  diffusible.  Sulphuretted  hy- 
drogen, in  proportion  as  it  is  set  free,  must  at  once  diffuse  into 
the  blood.  Planer  injected  into  the  rectum  of  dogs  sulphu- 
retted hydrogen  diluted  with  hydrogen,  and  observed  toxic 
symptoms  within  one  or  two  minutes.  When,  in  certain  proc- 
esses of  disease,  abnormal  decomposition  takes  place  in  the 
contents  of  the  bowel,  it  is  possible  that  a  large  quantity  of 
sulphuretted  hydrogen  may  be  developed.  In  the  artificial  di- 
gestion of  fibrin  by  pancreatic  juice,  without  excluding  bacteria, 
Kunkel  found  that  the  gases  contained  as  much  as  1.9  per  cent, 
of  HgS.  It  is  possible  that  in  the  headache,  vertigo,  and  nau- 
sea frequently  accompanying  gastric  and  intestinal  catarrh  and 
persistent  constipation,  poisoning  by  sulphuretted  hydrogen 
plays  a  part.  Senator^  communicates  the  following  case,  which 
he  regards  as  undoubtedly  one  of  poisoning  by  sulphuretted 
hydrogen.  He  succeeded  in  finding  sulphuretted  hydrogen  in 
the  urine  of  a  patient  suffering  from  acute  intestinal  catarrh,  as 
it  distinctly  gave  a  brown  color  to  a  visiting-card  which  con- 
tained lead.  The  eructations  of  the  patient  caused  a  distinct 
odor  of  sulphuretted  hydrogen.  He  also  had  repeated  attacks 
of  vertigo,  accompanied  by  epigastric  oppression  and  a  dark 
complexion.  It  is  stated  that  persons  engaged  in  the  emptying 
of  cesspools,  and  exposed  to  sulphuretted  hydrogen  gas,  have 
experienced  similar  symptoms. 

We  have  at  present  little  certain  knowledge  as  to  what  be- 
comes of  the  absorbed  hydrogen  and  marsh-gas.  They  either 
become  oxidized  or  reappear  in  the  exhaled  air.  An  experi- 
ment made  in  Zuntz's  ^  laboratoiy  in  Berlin,  with  a  tracheoto- 
mized  rabbit  showed  that  the  air  exhaled  by  these  animals  in- 
variably contains  hydrogen,  and  generally  marsh-gas  as  well — 
to  a  greater  extent  even  than  the  gases  voided  during  the  same 
period  per  anum.  It  has  not  yet  been  determined  whether 
all  hydrogen  and  all  marsh-gas  which  are  absorbed  from  the 
intestine  reappear  in  the  expired  air,  or  whether  a  part  is  oxi- 
dized in  the  body.  The  decision  of  this  question  would  be  of 
great  interest  for  the  theory  of  internal  respiration.  (Com- 
pare p.  238.) 

The  quantitative  composition  of  intestinal  gases  necessarily 

1  Senator,  Berlin.  Min,  WochcTisch.,  Jahrg.  v.  p.  254 :  1868. 

2B.  Tacke,  "  üeber  die  Bedeutung  der  brennbaren  Gase  im  thierischen 
Organismus,"  Inaug.  Dissert. :  Berlin,  1884.  Also  Ber.  d.  deutsch,  ehem.  Ges., 
vol.  xvii.  p.  1827  :  1884. 


280 


LECTURE    XVIII 


varies  greatly  according  to  the  diet  aud  the  condition  of  the  en- 
tire digestive  apparatus,  and  especially  according  to  the  extent 
to  which  fermentation  can  be  resisted.  Thus  for  instance  Ruge 
found  in  the  intestinal  gases  of  the  same  person  : — 


After  milk  diet. 

After  four  days' 

dietof  leguminosse 

only. 

After  three 
days'  diet  of 
meat  only. 

Oxygen 

36.71 
54.23 

9.06 

18.96 
4.03 
55.94 
21.05 
Trace 

64.41 

Hydrogen 

0.69 

CH, 

COj 

26.45 
8.45 

HjS 

Tappeiner  ^  found  that  the  gases  removed  half  an  hour  after 
death  from  the  corpse  of  a  man  who  had  been  executed,  exhib- 
ited the  following  composition  : 


stomach. 

Ileum. 

Colon. 

Bectum, 

Oxygen      

Nitrogen 

Hydrogen 

CH, 

COj 

9.19  \ 

74.26/ 

0.08 

0.16 

16.31 

67.71 
3.89 

28.4 

17.46 
0.46 
0.06 

91.92 



62.76 

0.9 
36.4 

*  Tappeiner,  Arb.  a.  d.  patholog.  Inst.  d.  München,  vol.  i.  p.  226 :  1886. 


LECTURE   XIX 

THE    NITROGENOUS    END-PRODUCTS    OF    METABOLISM 
HIPPURIC    ACID,    UREA,    CREATIN 

The  examiriation  of  the  processes  of  respiration  has  shown 
us  that  the  bulk  of  the  carbon  is  eliminated  from  our  body  by 
the  lungs  as  carbonic  acid.  The  remainder  of  the  carbon  takes 
a  different  course.  It  quits  our  body  in  combination  with  the 
bulk  of  the  nitrogen,  in  the  form  of  a  series  of  compounds  very 
rich  in  nitrogen,  through  the  kidneys.  Among  these  nitrog- 
enous end-products  the  chief  in  man  are  urea,  uric  acid, 
hippuric  acid,  creatin,  and  Creatinin.  A  considerable  portion 
of  nitrogen  appears  in  urine  as  an  inorganic  compound — as  a 
salt  of  ammonia. 

We  will  now  pursue  the  origin  of  these  end-products  in  the 
animal  body  as  far  as  the  present  state  of  our  knowledge 
permits.  We  will  begin  with  hippuric  acid,  because  the 
origin  of  this  compound  has  been  more  carefully  studied  and  is 
better  known  than  that  of  any  of  the  other  nitrogenous 
end-products.  The  constitution  of  hippuric  acid  is  accurately 
known.  The  following  mode  of  preparation  makes  it  very 
clear : — 

CgHj  — CO  — N<       +CH2CI  — COOH  = 
Benzamide.  Monochloracetic  acid. 

CjHj  — CO  — N<  +C1 

^CHj- COOH 

Hippuric  acid. 

If  we  boil  hippuric  acid  with  strong  mineral  acids  or  with 
alkalies,  or  subject  it  to  the  action  of  ferments,  it  splits  up 
with  hydration  into  benzoic  acid  and  amido-acetic  acid 
(glycocol). 

281 


282  LECTURE    XIX 

CfiHj  —  CO  —  N<  +  HP  = 

\CHj  — COOH 

Hippuric  acid. 

/^ 
CgH.  —  COOH  +  H  —  N< 

NdHj  — COOH 
Benzoic  acid.  Glycocol. 

Hippuric  acid  is  again  formed  with  dehydration,  from  these  two 
products  of  its  decomposition,  if  they  are  allowed  to  act  upon 
one  another  at  a  high  temperature  and  under  increased  pressure. 
To  effect  this  they  are  inserted  dry  into  a  glass  tube,  the  ends 
of  which  are  fused,  and  the  tube  is  kept  at  a  temperature  of 
160°  C.  for  twelve  hours.^ 

Hippuric  acid  is  also  formed  in  the  animal  body  by  the 
combination  of  benzoic  acid  and  glycocol.  If  benzoic  acid  is 
introduced  into  the  stomach  of  an  animal  or  a  human  being,  it 
reappears  as  hippuric  acid  in  the  urine.  Doubtless  the  gly- 
cocol used  in  its  formation  arises  from  the  decomposition  of 
the  Proteids  of  the  tissues.  Free  glycocol  has  certainly  not 
as  yet  been  proved  to  exist  in  animals.  As  little  are  we  able 
to  obtain  it  by  the  artificial  decomposition  of  proteid,  but  we 
know  that  the  immediate  derivatives  of  proteid,  the  collagenous 
substances,  when  decomposed  either  by  ferments,  by  acids  or 
by  alkalies,  readily  yield  glycocol.  In  combination  with  an 
acid  glycocol  also  appears,  as  we  have  seen,  in  bile  as  glyco- 
cholic  acid. 

Hippuric  acid  is  also  constantly  found  in  the  urine  of 
the  herbivora,  without  the  artificial  administration  of  benzoic 
acid.  The  numerous  aromatic  compounds  which  are  contained 
in  the  tissues  of  plants,  and  which  in  the  animal  body  are  con- 
verted by  oxidation  into  benzoic  acid,  evidently  yield  the  ma- 
terial for  its  formation.  However,  small  quantities  of  hip- 
puric acid  may  be  found  in  the  urine  of  dogs  fed  only  upon 
meat,  and  also  during  inanition.^  In  this  case  the  benzoic  acid 
is  formed  from  the  aromatic  radicals  which  are  contained  in  the 
proteid  molecule.^ 

The  amount  of  hippuric  acid  contained  in  the  urine  of  man 
in  twenty-four  hours  is  generally  less  than   1  grm.;  but  after 

^  Dessaignes,  Journ.  Pharm,,,  vol.  xxxii.  p.  44  :  1857. 

^E.  Salkowski,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  xi.  p.  500 :  1878. 

^E.  and  H.  Salkowski,  ibid.,  vol.  xii.  pp.  107,  648,  653:  1879;  Zeitschr.  f. 
physiol.  Cliem.,  vol.  vii.  p.  161:  1882;  E.  ^ViWioviski,  Zeitschr.  f.  physiol.  Chem., 
vol.  ix.  p.  229  :  1885.  Compare  also  Tappeiner,  Zeitschr.  f.  Biolog.,  vol.  xxii.  p. 
236 :  1886 ;  and  E.  Baas,  Zeitschr.  f.  physiol.  Chem.,  vol.  xi.  p.  485  :  1887. 


NITROGENOUS    END-PEODUCTS    OF    METABOLISM  283 

the  consumption  of  certain  berries  and  fruits  it  amounts  to  sev- 
eral grammes. 

The  fact  that  benzoic  acid  introduced  into  the  stomach 
reappears  as  hippuric  acid  in  the  urine  was  discovered  as  early 
as  1824  by  Wöhler.^  This  discovery  was  afterwards  confirmed 
by  numerous  experiments,  and  excited  some  attention,  for  it 
was  the  first  synthetic  process  which  was  proved  to  occur  in  the 
animal  body.  Since  then  a  long  series  of  other  syntheses  have 
been  discovered  in  the  animal  body.  I  need  only  remind  my 
readers  of  the  formation  of  the  conjugated  sulphuric  acids  and 
glycuronic  acids,  and  of  the  formation  of  glycogen  from  sugar. 
It  is  probable  that  the  formation  of  proteid  from  peptone  be- 
longs to  this  category.  We  shall  soon  become  acquainted  with 
other  synthetic  processes. 

There  are  two  reasons  why  these  synthetic  processes  in  the 
animal  body  have  excited  the  interest  of  physiologists  and 
chemists  during  the  last  twenty  years :  in  the  first  place,  these 
facts  were  in  contradiction  to  the  dominant  doctrine  of  Liebig 
with  regard  to  the  universal  contrast  between  the  metabolic 
processes  in  plants  and  in  animals ;  in  the  second  place,  the 
syntheses  in  animals  are  an  unsolved  problem  to  chemists, 
although  it  is  the  rapid  progress  in  our  knowledge  of  the 
syntheses  of  organic  compounds  which  constitutes  the  greatest 
triumph  of  modern  chemistry.  We  are  already  able  artificially, 
to  build  up,  atom  for  atom,  out  of  their  elements,  a  series  of 
organic  compounds,  some  of  a  very  complex  character.  We 
no  longer  doubt  that  all  the  rest,  even  the  most  complex,  will 
be  thus  produced ;  it  is  merely  a  question  of  time.  Still,  this 
in  no  way  represents  the  synthetic  processes  in  the  living  cell, 
for  all  our  artificial  syntheses  can  only  be  achieved  by  the 
application  of  forces  and  agents  which  can  never  play  a  part  in 
vital  processes,  such  as  extreme  pressure,  high  temperature, 
strong  galvanic  currents,  concentrated  mineral  acids,  free 
chlorin — factors  which  are  immediately  fatal  to  a  living  cell. 

Thus  we  have  seen  that  the  artificial  synthesis  of  benzoic 
acid  and  glycocol  to  hippuric  acid  could  only  be  induced  by 
heating  both  substances  in  a  dry  condition,  in  a  closed  tube,  to 
a  temperature  of  160°  C.  This  implies  extreme  pressure, 
extreme  temperature,  and  absence  of  water.  The  very  reverse 
is  the  case  in  the  animal  body,  where  we  find  water  in  every 
tissue,  and  the  ordinary  atmospheric  pressure  and  temperature 
in  every  cell.  Even  cold-blooded  animals  form  hippuric  acid. 
It  follows  that  the  animal  body  has  command  of  ways  and 

^Berzelius,  "Lehrbuch  der  Chemie,"  translated  by  Wöhler,  vol.  iv.  p.  376; 
Vote.  Dresden,  1831. 


284  LECTURE    XIX 

means  of  a  totally  diiferent  character,  by  which  the  same 
object  is  achieved.  An  inquiry  into  these  would  be  of  extreme 
interest  to  the  chemist  and  to  the  physiologist ;  the  former 
would  thus  obtain  new  methods  for  rising  to  still  more  com- 
plicated combinations,  and  the  physiologist  would  be  enabled  to 
explain  many  of  the  most  obscure  processes  in  metabolism. 

For  this  reason,  Schmiedeberg  and  I  conjointly  ^  resolved  to 
study  the  conditions  under  which  the  synthesis  of  hippuric  acid 
takes  place  in  the  animal  body. 

In  order  to  be  able  to  trace  benzoic  and  hippuric  acids 
through  the  tissues  of  the  animal  body,  we  required  above  all, 
a  precise  method  for  their  detection  and  estimation.  This  we 
succeeded  in  obtaining  after  many  experiments.  We  now 
possess  a  method^  which  enables  us  to  separate  these  acids 
from  all  other  constituents  of  the  animal  body,  and  to  weigh 
them  in  a  pure  crystalline  form  without  any  appreciable  loss. 

We  had  next  to  determine  in  what  organs  and  in  what 
tissues  the  synthesis  takes  place.  We  naturally  thought  first 
of  the  liver.  It  is  known  that  here  another  acid,  conjugated 
with  glycocol  (glycocholic  acid),  is  formed  ;  besides,  synthetic 
processes  have  often  been  assigned  to  the  liver.  If  this  view 
were  correct,  the  removal  of  the  liver  must  cause  the  benzoic 
acid  introduced  into  the  blood  to  circulate  unaltered  in  it,  and 
to  pass  out  by  the  kidneys  unchanged. 

This  experiment  could  not  be  carried  out  in  mammals 
because,  after  ligature  of  the  hepatic  vessels,  the  bulk  of  the 
blood  accumulates  in  the  portal  system,  and  the  circulation 
in  the  other  organs  is  almost  entirely  arrested.  Dogs 
die  from  thirty  to  fifty  minutes  after  this  operation.  It 
may  be  said  that  they  begin  to  die  as  soon  as  the  portal  vein 
is  tied. 

We  therefore  instituted  our  experiments  on  frogs.  They 
bear  the  extirpation  of  the  liver  very  well,  surviving  the  oper- 
ation for  three  or  four  days.  They  run  about  during  this  time 
with  almost  undiminished  vigor.  If  we  introduced  benzoic 
acid  into  the  dorsal  lymphatic  sac,  the  frogs  invariably  formed 
hippuric  acid,  which  was  more  copious  when,  in  addition  to 
benzoic  acid,  glycocol  was  injected.  Unless  benzoic  acid  was 
injected,  no  trace  of  hippuric  acid  was  ever  to  be  found  in  the 
tissues  or  in  the  secretions  of  the  frog.  It  follows  of  necessity 
that  the  liver  is  not  the  locality,  at  all  events  not  the  exclusive 
locality,  for  the  formation  of  hippuric  acid. 

'  Buuge  and  Schmiedeberg,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  vi.  p.  233  : 
1876. 

2  The  method  is  described,  loc.  cit.,  pp.  234-239. 


NITEOGENOUS    END-PEODUCTS    OF    METABOLISM  285 

We  then  thought  that  the  synthesis  might  possibly  occur 
in  the  kidney.  In  order  to  decide  this,  it  was  necessary  to 
have  recourse  to  warm-blooded  animals.  Dogs  survive  the 
ligature  of  the  vessels  of  both  kidneys  for  several  hours,  and 
the  circulation  in  their  other  organs  is  not  materially  affected. 
We  injected  glycocol  and  benzoic  acid  into  the  blood  of  dogs 
thus  operated  upon,  bled  them  to  death  after  three  or  four 
hours,  and  examined  the  blood  of  the  liver  and  muscles  for 
hippuric  acid  without  ever  finding  a  trace  of  it ;  we  found  only 
benzoic  acid.  It  therefore  appears  that  all  the  other  organs 
together  cannot,  without  the  kidneys,  combine  glycocol  and 
benzoic  acid,  and  that  the  kidney  is  the  locality  in  which  the 
synthesis  is  performed. 

A  sceptical  critic  will  not  be  satisfied  with  this  conclusion. 
There  is  still  room  for  objection.  The  ligature  of  the  kidneys 
may  be  regarded  as  so  violent  an  operation  as  to  produce  direct 
and  indirect  disturbances  of  all  kinds  in  all  parts  of  the 
organism.  We  must  therefore  admit  the  possibility  that  dis- 
turbances may  be  produced  in  tissues  with  which  we  are  as  yet 
unacquainted,  and  in  which  the  synthesis  is  effected. 

The  hope  remained  that  if  we  could  show  that  the  kidney, 
separated  from  other  organs,  was  able  to  produce  the  synthesis 
by  itself,  we  should  be  in  a  position  to  prove  that  the  formation 
of  hippuric  acid  took  place  in  that  organ.  This  hope  was 
realized.  We  bled  a  dog  to  death,  removed  the  kidneys,  added 
glycocol  and  benzoic  acid  to  the  defibrinated  blood,  and  con- 
veyed it,  under  an  approximately  normal  pressure,  through  the 
artery,  and  allowed  it  to  flow  out  of  the  veins  of  one  of  the 
kidneys.  The  blood  that  passed  out  of  the  vein  was  returned 
to  the  reservoir,  from  which  it  reentered  the  artery ;  and  this 
process  was  continued  for  several  hours.  Hippuric  acid  was 
invariably  found  in  the  blood  after  its  passage  through  the 
kidney,  and  in  the  fluid  which  during  its  passage  escaped  by 
the  ureter.  But  in  the  other  kidney,  and  in  a  portion  of  the 
blood  which  had  not  traversed  the  kidney,  no  trace  of  hippuric 
acid  could  at  any  time  be  discovered.  It  follows  that  hippuric 
acid  was  formed  in  the  excised  kidney.^ 

If  we  added  benzoic  acid  without  glycocol  to  the  blood 
that  was  passed  through  the  kidney,  the  quantity  of  hippuric 
acid  formed  was  small ;  but  it  was  considerable  when  glycocol 
was  mixed  with  it.  As  a  matter  of  fact,  the  two  ingredients 
had  entered  into  combination,  with  separation  of  water.  It 
was   indifferent   whether   we   raised    the   temperature   of  the 

1  Wilh.  Koehs  has  confirmed  these  results  by  a  series  of  careful  experiments 
in  Pfliiger's  laboratory  (Pfliiger's  Arch.,  vol.  xx.  p.  64 :  1879). 


286  LECTÜEE    XIX 

kidney  and  the  blood  to  the  temperature  of  the  body,  or 
cooled  it  to  that  of  the  room.  In  either  cases  the  synthesis 
was  effected.  It  was  remarkable  how  long  the  excised  kidney 
retained  the  faculty  of  forming  hippuric  acid.  In  one  of  our 
experiments  we  allowed  the  kidney  to  remain  for  forty-eight 
hours  in  an  ice-chest.  We  passed  the  blood  of  another  dog 
through  it,  which  had  been  obtained  twenty-four  hours  pre- 
viously ;  nevertheless  some  hippuric  acid  was  formed. 

We  now  inquired  whether  the  living  tissue  of  the  kidney  is 
essential  for  the  synthesis.  Does  the  result  depend  upon  the 
formed  elements  and  upon  a  definite  histological  arrangement, 
or  is  this  function  of  the  kidney  only  due  to  its  containing 
certain  chemical  substances?  In  the  latter  case,  it  might  be 
possible  to  isolate  these  substances,  and  then  to  effect  the  syn- 
thesis artificially. 

Accordingly  we  destroyed  the  renal  tissue.  We  chopped 
up  the  kidney  and  pounded  it  into  a  homogeneous  pulp.  To 
this  we  added  blood,  glycocol,  and  benzoic  acid,  and  allowed 
the  mixture  to  stand,  shaking  it  at  frequent  intervals.  We 
varied  the  experiment,  applied  different  temperatures,  provided 
a  copious  supply  of  oxygen,  but  we  never  succeeded  in  finding 
a  trace  of  hippuric  acid. 

This  experiment  was  repeated  in  Pfliiger's  laboratory  by 
Kochs.^  When  the  kidney  had  only  been  chopped  up,  Kochs 
discovered  minute  traces  of  hippuric  acid,  but  if  it  had  been 
not  only  chopped  up,  but  also  rubbed  up  "  in  a  mortar  with 
large  pieces  of  glass  "  to  an  almost  homogeneous  mass,  not  a 
trace  of  hippuric  acid  was  to  be  found ;  nor  was  it  met  with 
when  the  kidney,  before  being  chopped  up,  had  been  frozen  at 
-  20°  C,  and  thawed  at  40°. 

These  experiments  appear  to  prove  that  the  synthesis  is  due 
to  the  living  cells  of  the  kidney,  and  not  to  one  of  its  chemical 
components. 

We  now  inquired  whether  the  blood-corpuscles  are  essential 
for  the  production  of  the  synthesis.  We  therefore  conducted 
serum  which  had  been  deprived  of  all  cells  by  the  centrifugal 
machine,  together  with  glycocol  and  benzoic  acid,  through  the 
excised  kidney.  In  this  case  no  hippuric  acid  was  formed.  It 
follows  that  the  blood-corpuscles  also  take  an  active  part  in  the 
synthesis. 

We  now  proceeded  to  inquire  into  the  part  played  by  the 
blood-cells  in  this  process,  and  to  determine  whether  they  act 
only  as  oxygen-carriers. 

In  order  to  decide  this  question,  Schmiedeberg  and  Arthur 

1  Wilhelm  Kochs,  Pfliiger's  Arch.,  vol.  xx.  p.  70,  et  seq.:  1879. 


NITROGENOUS    END-PRODUCTS    OF    METABOLISM  287 

Hoffman^  conducted  blood  mixed  with  glycocol  and  benzoic 
acid,  and  in  which  the  oxygen  had  been  replaced  by  carbonic 
oxid,  through  the  kidneys.  The  result  was  that  no  hippuric 
acid  was  formed.  The  blood-cells  therefore  also  act  as  oxygen- 
carriers  in  the  synthetic  process,  but  whether  they  have  only 
this  function  remains  uncertain.  It  may  be  objected  that  the 
carbonic  oxid,  besides  driving  out  the  oxygen,  has  a  toxic 
effect  on  the  renal  cells.  The  following  experiment  of 
Schmiedeberg  and  Hoffman  goes  to  prove  that  certain  poisons 
do  deprive  the  cells  of  the  power  of  effecting  syntheses.  They 
conducted  blood,  to  which,  besides  glycocol  and  benzoic  acid, 
quinine  had  been  added,  through  the  kidneys.  Only  a  very 
small  quantity  of  hippuric  acid  was  subsequently  found.  It  is 
known,  from  the  investigations  of  C.  Binz,^  that  quinine  arrests 
the  ameboid  movements  of  the  cells.  The  same  influence  that 
kills  the  cell  likewise  deprives  it  of  the  capability  of  bringing 
about  syntheses. 

With  regard  to  the  locality  where  hippuric  acid  is  formed 
in  the  animal  body,  I  would  add  that  its  exclusive  formation  in 
the  kidney  is  only  proven  in  the  case  of  the  dog.  Schmiede- 
berg and  I  have  already  shown  that  frogs  form  hippuric  acid 
even  after  extirpation  of  the  kidney.  Salomon^  discovered 
subsequently  that  certain  mammals  do  not  form  hippuric  acid 
exclusively  in  the  kidney.  Salomon,  after  giving  benzoic  acid 
to  rabbits  which  had  been  deprived  of  their  kidneys,  found 
abundant  hippuric  acid  in  their  blood,  muscles,  and  liver. 

If  benzoic  acid  be  introduced  into  birds,  it  appears  in  the 
urine,  not  as  hippuric  acid,  but  combined  with  a  base,  which 
Jaff6*  described  as  Ornithin,  having  the  formula  CgH^2^2Ö2' 
It  is  probably  diamido-valerianic  acid.  Two  other  diamido- 
acids  were  discovered  later  by  Drechsel  among  the  products  of 
disintegration  of  proteids,  viz.,  diamido-acetic  acid  and  diamido- 
caproic  acid  or  lysin.  These  latter  have  hitherto  been  obtained 
only  outside  the  organism  by  the  artificial  hydrolysis  of  pro- 
teids, whereas  diamido-valerianic  acid  has  only  been  detected 
as  the  result  of  the  natural  decomposition  of  proteids  in  the 
body.  The  compound  of  benzoic  acid  and  Ornithin  has  been 
called  ornithuric  acid  by  Jaff§. 

But,  as  already  mentioned,  a  very  inconsiderable  portion  of 
the  nitrogen  in  human  beings  is  eliminated  as  hippuric  acid. 
The  bulk  of  it,  in  man  and  mammals,  appears  in  the  urine  as 

^  Arthur  Hoffman,  Arch.  f.  exper.  Path.  u.  Pharm,,  vol.  vii.  p.  239 :  1877. 
2  C.  Binz,  Arch.  f.  mikr.  Anat.,  vol.  iii.  p.  383  :  1867. 
*  Salomon,  Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  365. 

'^  JaSe,  Per.  d.  deutsch,  chem.  Ges.,  vol.  x.  p.  1925:  1877;  vol.  xi.  p.  406: 
1878.     Hans  Meyer,  ibid.,  vol.  x.  p.  1930  :  1877. 


288  LECTURE   XIX 

UEEA.  The  amount  of  urea  excreted  is  therefore  regarded  as 
an  index  of  the  consumption  of  proteid  in  the  body.  The 
greater  portion  of  nitrogen  is  introduced  in  the  form  of 
proteid.  Nearly  half  the  weight  of  urea  consists  of  nitrogen. 
The  100  grms.  of  proteid  daily  used  up  by  one  person  contain 
about  16  grms.  of  nitrogen,  to  which  34  grms.  of  urea  corre- 
spond. This  is  about  the  quantity  found  in  a  man's  urine 
during  twenty-four  hours. 

The  constitution  of  urea  is  known.  Its  formation  from 
carboxyl  chlorid  (COClj)  and  ammonia,  as  well  as  from  ethyl 
carbonate  and  ammonia,  undoubtedly  shows  that  urea  should  be 
regarded  as  the  amid  of  carbonic  acid,  Carbamid  [CO(HN2)2] . 
On  heating  with  acids  or  alkalies  or  by  the  action  of  ferments, 
urea  takes  up  two  molecules  of  water  and  is  converted  into  car- 
bonate of  ammonia.  Urea  is  a  neutral  compound,  capable  of 
crystallization  and  very  readily  soluble  in  water. 

How  does  urea  arise  from  proteid,  and  what  are  the  inter- 
mediate stages  ?  A  recapitulation  of  our  previous  remarks  on 
the  changes  of  proteid  in  the  body  may  not  be  out  of  place 
here.  It  was  shown  that  proteid  was  converted  by  the  digestive 
ferments  into  peptones ;  that  the  peptones  are  probably  prod- 
ucts of  decomposition  ;  and  that,  by  continued  action  of  the 
digestive  ferments  or  of  other  ferments  of  decomposition,  a 
part  of  the  nitrogen  is  split  off  in  the  form  of  amido-acids,  as 
amido-caproic  acid  or  leucin   [C5H,q(NH2)COOH]  ,  as  tyrosin, 

an    aromatic    amido-acid    lCgH^-(  p  it /-vrtr  \rir)r)Ti )  >   ^^^   ^s 

amido-succinic  acid  or  aspartic  acid  ^  [C2H3(NH2)(COOH2)] 
and  its  homologue,  glutamic  acid,  C3H.(NH2)(COOH)2.  The 
proteids  also  give  the  same  products  of  decomposition  on  boil- 
ing with  acids  or  with  alkalies."  We  have  moreover  seen  that 
a  portion  of  the  proteids  is  converted  in  the  animal  body  into 
collagenous  substances  which,  under  the  same  conditions  as 
the  ])roteids,  produce  amido-acids,  and  especially  leucin  and 
glycocol.^ 

1  Radziejewski  and  E.  Salkowski,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  vii.  p. 
1050:  1874;  W.  von  Knieriem,  Zeitschr.f.  Biolog.,  vol.  xi.  p.  198  :  1875. 

^Hlasiwetz  and  Habermann,  Ann.  d.  Chem.  u.  Pharm.,  vol.  clxix.  p.  150: 
1873 :  E.  Schulze,  J.  Barbieri  und  E.  Bossard,  Zeitschr.  f.  physiol.  Chem.,  vol. 
ix.  p.  63:  1884;  E.  Schulze  und  E.  Bossard,  ibid.,  vol.  x.  p.  134:  1885;  M.  P. 
Schiitzenberger,  Bull,  de  la  SociHe  chim.,  vol.  xxiii.  pp.  161,  193,  216,  242,  385, 
433;  vol.  xxiv.  pp.  2,  145:  1875;  vol.  xiv.  p.  147:  1876;  Schützenberger  et  A. 
Bourgeois,  C'ompt.  rend.,  vol.  Ixxxii.  p.  262 :  1876.  Compare  also  R.  Maly, 
Sitzungsber.  d.  k.  Akad.  d.  W.  in  Wien.,  Math.  nat.  CI.,  vol.  xci.  part  ii.,  Feb., 
1885;  vol.  xcvii.  part  ii.,  March,  1888;  and  vol.  xcix.  part  ii.,  Jan.,  1889. 

^Nencki,  "  Ueber  die  Zersetzung  der  Gelatine  und  des  Eiweisses  bei  der 
Fäulniss  mit  Pankreas  "  :  Berlin,  1876.  .Jules  Jennaret,  i/bitrn.. /.  jpra/jf.  Chem., 
N.  F.,  vol.  XV.  p.  353:  1877  (from  Nencki's  laboratory). 


UREA  289 

More  recently  a  number  of  basic  substances  have  been  dis- 
covered among  the  products  of  disintegration  of  proteids.  As 
we  have  already  mentioned,  Drechsel  found  diamido-acetic 
acid/  diamido-caproic  acid  or  lysin/  and  a  body  to  which  he 
gave  the  name  of  lysatin  and  which  has  been  since  found  to 
consist  of  a  mixture  of  lysin  with  another  base,  arginin.^  This 
substance,  together  with  histidin,^  was  first  discovered  by 
Hedin. 

Arginin  (CgHj^N^Oj)  and  histidin  (CgHgNgO^)  had  already 
been  discovered  by  Kossel,  together  with  lysin,  among  the 
decomposition  products  of  certain  bases  which  occur  in  the 
spermatozoa  of  certain  fish.  Miescher^  had  previously  found 
a  base  of  the  composition  CjgHggNgOg  in  the  spermatozoa  of 
Rhine  salmon  and  had  given  it  the  name  of  protamin.  Kossel  ® 
found  similar  bases  in  the  spermatozoa  of  other  Salmonidse  as 
well  as  of  the  sturgeon  and  herring.  It  is  remarkable  that  the 
Protamins  give  the  most  constant  proteid  reaction,  viz.,  the 
biuret  reaction. 

These  facts  suggest  that  all  these  nitrogenous  substances 
might  be  regarded  as  the  precursors  of  urea.  So  far  only 
the  amido-acids  have  been  the  subject  of  direct  experiment. 
Schnitzen  and  Nencki^  administered  leucin  and  glycocol  to 
dogs,  and  found  that  these  compounds  did  not  reappear  in  the 
urine,  but  that  there  was  a  corresponding  increase  of  urea. 
Salkowski,^  on  repeating  these  experiments,  fully  confirmed  these 
results.  Knieriem  ^  showed,  by  a  similar  method  of  research, 
that  aspartic  acid  is  also  converted  into  urea. 

But  even  these  facts  tend  but  little  to  the  elucidation  of  the 
origin  of  urea.  It  is  only  the  smallest  part  of  urea  which  can 
be  formed  from  amido-acids.  This  is  seen  by  a  glance  at  the 
empirical  formula  of  proteids.    We  have  shown  (pp.  49-51)  that 


'  E.  Drechsel,  Ber.  d.  k.  sack.  Ges.  d.  Wissensch.,  p.  115  :  1892. 

*E.  Drechsel  and  R.  Krüger,  £er.  d.  deutsch,  ehem.  Ges.,  vol.  ixv.  p.  2454: 
1892. 

ä  Hedin,  Zeitschr.  f.  physiol.  Chem.,  vol.  xx.  p.  186 :  1895 ;  vol.  xxi.  p.  155  : 
1896.     Compare  also  E.  Schulze  and  E.  Steiger,  ibid.,  vol.  xi.  p.  43  :  1887. 

*  Hedin,  Zeitschr.  f.  physiol.  Chem.,  vol.  xxii.  p.  191:  1896.  Compare  M. 
Bauer,  ibid.,  vol.  xxii.,  p.  284:  1896. 

s  Miescher,  Verhandl.  d.  naturf.  Ges.  in  Basel,  p.  138 :  1874.  J.  Piccard, 
Ber.  d.  deutsch,  chem.  Ges.,  vol.  vii.  p.  1714:  1874.  Posthumous  paper  of 
Miescher,  edited  by  O.  Schmiedeberg,  Arch.  f.  exper.  Bath.  u.  Pharm.,  vol. 
xxxvii.  p.  100 :  1896. 

8  Kossel,  Sitzungsber.  d.  Ges.  z.  Befdrd.  d.  ges.  Naturwissensch.  z.  Marburg, 
No.  5,  p.  56 :  July,  1897. 

'  Schultzen  and  Nencki,  Zeitschr.  f.  Biolog.,  vol.  viii.  p.  124 :  1872. 

"E.  Salkowski,  Zeitschr.  f.  physiol.  Chem.,  vol.  iv.  p.  100:  1879. 

**  W.  von  Knieriem,  Zeitschr.  f.  Biolog.,  vol.  x.  p.  279 :  1874. 

19 


290  LECTÜEE    XIX 

the  following  formulse  may  be  deduced  from  the  most  reliable 
analyses  of  the  purest  preparations  of  proteids. 

Egg-albumin,  CawHjjjNsjOegSj. 

Proteid  in  hemoglobin  from  horse.  CjgoHioggNjioOjiiSj. 

Proteid  in  hemoglobin  from  dog.  CYjeHnnNig^OanSj. 

Globulin  from  pumpkin  seeds.  C292H4giN9o083S2. 

"We  see  that  there  is  not  nearly  sufficient  carbon  in  the  proteid 
to  permit  of  all  the  nitrogen  issuing  as  an  amido-acid.  In  the 
various  kinds  of  proteid,  from  three  to  four  atoms  of  carbon  go 
to  one  atom  of  nitrogen  ;  in  aspartic  acid,  four  atoms  of  carbon 
to  one  of  nitrogen ;  in  leucin,  six ;  and  in  tyrosin,  as  many  as 
nine.  Glycocol  indeed  contains  only  two  atoms  of  carbon  to 
one  of  nitrogen.  But  it  is  questionable  whether  it  is  this  amido- 
acid  which  is  formed  in  especially  large  quantity  from  the  proteid 
in  the  animal  body.  As  stated,  it  cannot  be  obtained  from  the 
proteid  outside  the  organism,  but  only  if  the  proteid  has  been 
previously  changed  by  the  vital  process  in  the  animal  into  a 
collagenous  substance  ;  and  it  is  only  the  smallest  portion  of  the 
proteid  of  the  food  which  undergoes  this  conversion.  It  must 
also  be  taken  into  consideration  that  the  proteid  in  the  animal 
body  also  yields  products  of  decomposition  free  from  nitrogen 
and  very  rich  in  carbon.  What  follows  will  make  it  apparent 
that  fat  and  glycogen  can  be  formed  in  the  animal  body  from 
proteid.  We  are  thus  obliged  to  conclude  that  the  largest  por- 
tion of  the  nitrogen  is  split  off  from  the  proteid  molecule  as  a 
compound  containing  very  little  carbon. 

It  is  possible  that  a  part  of  the  urea  in  the  animal  body  is 
separated  directly  from  the  proteid  as  a  neutral  compound. 
But  it  is  also  possible  that  ammonia  and  carbonic  acid  split 
off  from  the  proteid,  subsequently  combining,  with  elimination 
of  water,  to  form  urea.  This  would  be  a  process  completely 
analogous  to  that  involved  in  the  formation  of  hippuric  acid. 
As  monobasic  benzoic  acid  unites  with  a  molecule  of  a  sub- 
stituted ammonia  (glycocol),  losing  one  molecule  of  water,  to 
form  hippuric  acid,  so  dibasic  carbonic  acid  unites  with  two 
molecules  of  ammonia,  losing  two  molecules  of  water,  to  form 
urea — 


^=  o  +  2NH3  =  2H2O  +0=0 

OH  \NH, 


•^ 


The  conversion  of  the  amido-acids  into  urea  may  be  thus  repre- 
sented :  they  are  first  split  up  and  oxidized  into  carbonic  acid 


UREA  291 

and  ammonia,  and  in  this  state  yield  the  material  for  the 
formation  of  urea.  In  any  case,  we  have  to  deal  with 
another  synthetic  process,  for  the  leucin  and  glycocol  contain 
but  one  atom  of  nitrogen  in  the  molecule,  whereas  urea  has 
two. 

The  supposition  that  carbonate  of  ammonia  was  the  ante- 
cedent of  urea  was  based  upon  the  following  observations  of 
Buchheim  and  his  pupil  Lohrer.^  The  latter  took  3  grms.  of 
ammonia  in  the  form  of  citrate,  expecting  that  it  would  behave 
in  the  body  like  citrate  of  potash  or  soda,  which  are  known  to 
pass  into  the  urine  as  carbonates  of  potash  or  soda,  and  to 
render  the  urine  alkaline.  But  this  did  not  happen.  The 
urine  remained  acid.  The  carbonate  of  ammonia  formed  must 
therefore  have  been  converted  into  a  neutral  compound.  It 
was  readily  assumed  that  urea  had  been  formed. 

In  order  to  decide  the  question  whether  ammonia  is  con- 
verted in  the  animal  body  into  urea,  careful  experiments  on 
the  metabolic  changes  were  made  by  Knieriem^  on  dogs  and 
on  human  beings,  and  by  Salkowski^  on  dogs  and  on  rabbits. 
The  experiments  made  on  rabbits  gave  results  which  were 
quite  definite :  after  the  administration  of  chlorid  of  ammonia, 
the  excretion  of  ammonia  was  scarcely  increased  at  all,  whereas 
that  of  urea  was  increased.  The  experiments  on  human  beings 
and  on  dogs  were  not  so  definite.  Part  of  the  ammonia 
appeared  unaltered  in  the  urine,  and  it  remained  doubtful 
whether  the  extra  excretion  of  urea  was  to  be  ascribed  to  the 
ammonia  administered,  or  to  an  indirect  increase  of  proteid- 
decomposition  produced  by  the  ammonia.  This  difference  in 
its  action  in  rabbits  as  compared  with  human  beings  and  dogs 
may  be  explained  as  follows.  The  hydrochloric  acid  of  the 
chlorid  of  ammonia  introduced,  by  its  strong  affinity  for 
ammonia,  prevents  the  union  of  the  latter  with  the  carbonic 
acid  to  form  urea.  Now,  in  the  organism  of  herbivora  this 
hindrance  is  overcome,  because  the  vegetable  food  yields  an 
alkaline  ash;  carbonate  of  potash  is  also  formed  in  the 
organism  by  combustion;  this,  together  with  the  chlorid  of 
ammonia,  is  converted  into  chlorid  of  potash  and  carbonate  of 
ammonia,  which  latter  is  changed  into  urea.  The  mixed  diet 
of  human  beings  and  of  dogs  in  Knieriem's  and  Salkowski's 
experiments  would  necessarily  give  a  feebly  acid  ash;  the 
conversion  of  the   ammonia   into  urea  was  therefore  not    so 

^  Julius  Lohrer,  "  Ueber  den  Uebergang  der  Ammoniaksalze  in  den  Harn," 
Inaug.  Dissert.  Dorpat,  1862,  pp.  36,  37. 

2  von  Knieriem,  Zeitschr.  f.  Biolog.,  vol.  x.  p.  263 :  1874. 
^  E.  Salkowski,  Zeitschr.  f.  physiol.  Chem.,  vol.  i.  p.  1 :  1877. 


292  LECTURE  XIX 

complete.  Feder/  who  experimented  with  chlorid  of  ammonia 
upon  fasting  dogs,  recovered  all  the  ammonia  from  the  urine. 
For  the  fasting  dog  is  nourished  by  some  of  the  proteid  of  its 
tissues,  and  a  great  deal  of  sulphuric  acid  is  set  free.  This 
prevents  the  ammonia  from  uniting  with  the  carbonic  acid. 
Fr.  Walter^  and  Coranda^  showed  the  excretion  of  ammonia 
to  be  considerably  augmented  in  dogs  and  in  man  after  the 
administration  of  hydrochloric  acid.  The  latter  impedes  the 
normal  formation  of  urea.  The  administration  of  carbonate 
of  soda  diminishes  the  normal  excretion  of  ammonia.*  For 
this  reason  the  experiments  on  the  formation  of  urea  were 
repeated  in  Schmiedeberg's  laboratory/  but  the  ammonia  was 
not  administered  in  combination  with  strong  mineral  acids,  but 
simply  as  carbonate.  The  dog  swallowed  the  carbonate  of 
ammonia  wrapped  in  meat  readily  enough ;  in  this  manner  3 
grms.  NHg  were  administered  to  the  animal  on  two  successive 
afternoons.  The  excretion  of  ammonia  in  the  urine  was  not 
found  to  be  augmented,  but  there  was  an  increase  of  urea,  and 
the  urine  remained  acid.  Thus  there  can  be  no  doubt  that 
carbonate  of  ammonia  is  converted  into  urea. 

Hoppe-Seyler  ^  and  Salkowski^  have  arrived  at  other 
views  concerning  the  origin  of  urea.  They  regard  cyanic 
acid  as  the  immediate  precursor  of  urea,  and  DrechseP 
considers  that  urea  arises  from  carbamate  of  ammonia.  This 
last  opinion  is  not  at  variance  with  the  idea  that  urea 
originates    in    carbonate    of    ammonia.      For    carbamate    of 

ammonia   <  C=0  V    stands  midway  between  carbonate 

I    \0(NH,)j 

^  Feder,  Zeitschr.  f.  Biolog.,  vol.  xiii.  p.  256  :  1877. 

2  Fr.  Walter,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  vii.  p.  148 :  1877. 

3  Coranda,  ihid.,  vol.  lii.  p.  76  :  1880. 

"^Munk,  Zeitschr.  /.  physiol.  Chem.,  vol.  ii.  p.  29:  1878;  E.  Hallervorden, 
Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  x.  p.  124:  1879. 

^Hallervorden,  loa.  cit.,  whose  results  have  been  confirmed  by  Feder  and 
Voit,  Zeitschr.  f.  Biolog.,  vol.  xvi.  p.  177  :  1880. 

*  Hoppe-Seyler,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  vii.  p.  34:  1874;  and 
"Physiologische  Chemie,"  pp.  809,  810:  Berlin,  1881. 

■^  E.  Salkowski,  Centralbl.  f.  d.  med.  Wissensch.,  p.  913:  1875;  Zeitschr.  f. 
physiol.  Chem.,  vol.  i.  pp.  26-42  :  1877.  Compare  also  Schmiedeberg's  objections 
in  the  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  viii.  p.  4,  et  seq.:  1878;  and 
Schroder's,  ibid.,  vol.  xv.  pp.  399,  400 :  1882. 

*  E.  Drechsel,  Ber.  d.  sächs.  Ges.  d.  Wissensch.,  p.  171 :  1875 ;  Journ.f.prakt. 
Chem.,  N.  F.,  vol.  xii.  p.  417  :  1875 ;  vol.  xvi.  pp.  169,  180 :  1877;  vol.  xxii.  p. 
476 :  1880.  Compare  also  the  objections  raised  by  Franz  Hofmeister,  Pfliiger's 
Arch.,  vol.  xii.  p.  337  :  1876.  Considerable  difficulties,  which  have  not  yet  been 
successfully  overcome,  are  met  with  in  the  attempt  to  detect  and  determine 
quantitatively  the  carbamic  acid  in  the  urine  and  tissues.  Compare  Hahn  and 
Nencki,  Arch.  d.  8c.  bioL,  vol.  i.  p.  447 :  St.  Petersburg,  1892. 


ußEA  293 

of   ammonia    <  C=0  V    and   urea    ^  C=0       V.       By 

i    \0(NHjj  l    \nhJ 

eliminating  one  molecule  of  water,  carbonate  of  ammonia  yields 
carbamate  of  ammonia ;  by  elimination  of  a  second  molecule, 
urea.  As  it  would  lead  me  too  far  to  enter  into  these  theories 
at  greater  detail,  I  refer  the  reader  to  the  interesting  original 
works  that  deal  with  the  matter. 

The  most  complete  and  reliable  researches  as  to  the  locality 
in  which  urea  is  generated  have  been  made  by  W.  von 
Schröder.^  He  extirpated  both  kidneys  in  a  dog,  and  took  a 
specimen  of  the  blood  from  the  carotid  immediately  after  the 
operation.  The  dog  was  bled  to  death  twenty-seven  hours 
afterwards.  The  quantity  of  urea  in  each  sample  of  blood 
was  determined.^  In  the  first  case  it  amounted  to  0.5  per 
thousand ;  in  the  second,  to  2  per  thousand.  The  urea  in  the 
blood  is  therefore  increased  fourfold  by  the  extirpation  of  the 
kidneys,  and  it  follows  that  the  kidneys  cannot  be  the  only 
place  where  urea  is  formed.^ 

But  the  possibility  still  remained  that  urea  was  formed  in 
the  kidney  as  well.  Schröder  therefore  conducted  blood,  to 
which  carbonate  of  ammonia  had  been  added,  through  the 
excised  kidneys.  The  amount  of  urea  in  the  blood  remained 
the  same,  both  before  and  after  it  had  been  passed  through  the 
kidneys.  As  the  formation  of  urea  from  carbonate  of  ammonia 
is  a  process  entirely  analogous  to  that  of  the  formation  of 
hippuric  acid  from  glycocol  and  benzoic  acid,  and  as  the 
excised  kidney  still  brings  about  the  latter  synthesis,  this 
experiment  renders  it  extremely  probable  that  carbonate  of 
ammonia  does  not,  in  normal  conditions,  undergo  conversion 
into  urea  in  the  kidneys. 

Urea  is  therefore  not  formed  in  the  kidneys  but  merely 
excreted  by  them.  But  where  is  it  formed  ?  As  the  muscles 
constitute  40  per  cent,  of  the  whole  weight  of  the  body,  it  was 
natural  to  think  of  them  first.     The  compound,  which  forms 

1  W.  von  Schröder,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xv.  p.  364:  1882; 
and  vol.  xix.  p.  373  :  1885. 

2  The  admirable  care  with  which  the  methods  of  determining  the  urea  were 
controlled  and  carried  out  renders  Schroder's  researches  so  valuable,  and  raises 
them  far  above  those  of  his  predecessors.  In  the  decisive  experiments  the  urea 
was  weighed  in  pure  crystals,  which  were  subsequently  analyzed  to  test  their 
purity.    The  method  is  described  loc.  cit.,  pp.  367-377. 

^  The  results  of  previous  work  are  in  harmony  with  this,  especially  those  of 
Prevost  and  Dumas  in  the  Ann.  de  Chim.  et  de  Phys.,  vol.  xxiii.  p.  90 :  1823.  An 
account  of  the  earlier  literature  is  given  by  Voit,  Zeitschr.f.  Biolog.,  vol.  iv.  p. 
116,  et  seq. :  1868;  and  by  Schröder,  loc.  cit.,  pp.  364,  365. 


294  LECTUEE   XIX 

the  bulk  of  the  nitrogenous  end-products,  might  arise  in  the 
muscles.  Schröder  therefore  conducted  blood  impregnated  with 
carbonate  of  ammonia  through  the  hind  quarters  of  a  dog 
which  had  been  bled  to  death.  The  blood  was  introduced  into 
the  abdominal  aorta  below  the  renal  arteries,  and  flowed  out 
of  the  inferior  vena  cava.  In  one  of  the  experiments  1100 
c.cms.  of  blood  were  passed  repeatedly  through  the  limbs,  so 
that  the  total  flow  during  4f  hours  amounted  to  40  liters. 
"During  the  first  four  hours  the  limbs  moved  spontaneously, 
obviously  from  the  stimulation  to  the  spinal  cord ;  its  irrita- 
bility continued  to  the  end  of  the  experiment.  If  one  electrode 
was  inserted  into  the  spinal  cord  and  the  other  applied  to  the 
leg,  tetanus  ensued.  A  part  of  the  spinal  cord  evidently  pre- 
served its  vitality,  for  stimulation  of  one  leg  produced  contrac- 
tion of  the  other."  But  the  amount  of  urea  in  the  blood  was 
exactly  the  same  before  and  after  the  passage  of  the  blood. 
The  conclusion  therefore  is  that  no  urea  is  formed  from  carbon- 
ate of  ammonia  in  the  muscles  and  tissues  of  the  body  ;  unless 
indeed  the  objection  were  raised  that  the  extremities  could  not 
be  regarded  as  being  under  normal  conditions  in  spite  of  the 
remarkable  way  they  appeared  to  retain  their  vital  properties. 

The  liver  was  the  next  organ  to  be  thought  of.  It  was  to 
be  expected  that  large  quantities  of  urea  could  be  formed  only 
in  a  large  organ.  There  are  various  reasons  for  believing 
that  extensive  metabolic  processes  go  on  in  the  liver,  the 
largest  of  the  glands.  Schröder  therefore  conducted  blood 
containing  carbonate  or  formate  of  ammonia  through  the  liver. 
The  organ  was  removed  from  a  small  dog,  whose  blood  was 
mixed  with  that  of  a  large  dog.  The  blood  was  introduced  into 
the  portal  vein,  and  flowed  out  of  the  vena  cava  above  the 
diaphragm.  The  hepatic  artery  was  closed.  After  the  blood 
had  been  allowed  to  pass  for  from  four  to  five  hours,  the 
urea  was  found  to  amount  to  between  double  and  treble  the 
previous  quantity.  If  blood  without  any  carbonate  of  am- 
monia was  conducted  through  the  liver,  the  amount  of  urea 
increased  but  little,  and  then  only  in  those  experiments  in 
which  the  liver  and  the  blood  were  taken  from  dogs  during 
digestion.  If  the  blood  and  liver  were  removed  from  fasting 
dogs,  and  carbonate  of  ammonia  was  not  mixed  with  the  blood, 
no  urea  was  formed  ;  but  this  occurred  directly  carbonate  of 
ammonia  was  added. 

These  results  of  Schroder's  have  been  confirmed  by  Salo- 
mon,^ who  made  his  experiments  on  herbivora  (sheep)  as  well 
as  on  dogs. 

*  W.  Salomon,  Virchow's  Arch.,  vol.  xcvii.  p.  149  :  1884. 


UREA  295 

Hence  it  follows  that  the  synthesis  of  carbonate  of  ammonia 
into  urea  takes  place  in  the  liver. 

Even  this  knowledge  however  does  not  advance  our  acquaint- 
ance with  the  precursors  of  urea.  The  antecedents  of  the  small 
amount  of  urea,  obtained  by  passing  through  the  liver  blood 
which  had  been  taken  from  dogs  during  digestion,  are  still 
unknown.  In  all  the  other  experiments  the  precursor  (carbon- 
ate of  ammonia)  was  artificially  introduced.  What  justification 
is  there  for  the  conclusion  that  carbonate  of  ammonia  is  also 
normally  the  precursor  of  urea  ? 

Schröder  based  his  views  on  this  subject  upon  pathological 
facts.  If  normally  urea  really  arises  in  the  liver  from  car- 
bonate of  ammonia,  we  should  expect  that  in  diseases  of  the 
liver  the  formation  of  urea  would  be  arrested,  and  that  a 
portion  of  the  precursors  would  pass  unchanged  into  the  urine. 
We  should  especially  anticipate  this  in  cirrhosis  of  the  liver, 
when  the  specific  hepatic  cells  are  pressed  upon  by  the  en- 
croaching connective  tissue,  become  atrophied,  and  in  great  part 
disappear. 

The  above  assumption  has  been  confirmed  by  observation. 
Investigators  have  found  that  in  interstitial  hepatitis  the  elimi- 
nation of  ammonia  is  increased  both  absolutely  and  relatively 
in  proportion  to  the  excretion  of  urea.^  Healthy  people  excrete 
from  0.4  to  0.9  grm.  of  ammonia  in  twenty-four  hours,  and  in 
cases  of  cirrhosis  it  rises  to  2.5  grms. 

It  is  thus  rendered  probable  that  part  of  the  urea  does  arise 
normally  from  carbonate  of  ammonia,  but  the  actual  quantity 
is  not  yet  known.  It  may  be  that  only  the  small  amount  of 
ammonia  produced  by  bacterial  putrefaction  in  the  intestines  is 
absorbed  by  the  blood  of  the  portal  vein  to  undergo  this  con- 
version in  the  liver  into  the  innocuous  urea.  (Compare  Lecture 
XXII.)  Ammonia  is  a  poison,  and  one  of  the  functions  of  the 
liver  is  the  prevention  of  ammonia  intoxication.  We  must 
therefore  acknowledge  the  possibility  that  the  bulk  of  the  urea 
takes  its  origin  from  another  source. 

The  question  as  to  the  part  played  by  the  liver  in  the 
formation  of  urea  might  be  definitely  decided  if  we  could 
succeed  in  keeping  mammals  alive  for  a  considerable  time  after 
complete  extirpation  of  the  liver,  or  at  any  rate  after  cutting 
this  organ  out  of  the  circulation.  I  have  already  mentioned 
(p.  284)  the  chief  difficulty  which  prevents  the  carrying  out 
of  this  operation,  viz.,  the  complete  stasis  which  occurs  in  the 

■^  Hallervorden,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xii.  p.  237 :  1880 ; 
Stadelmann,  Deutsch.  Arch.  f.  klin.  Ned.,  vol.  xxxiii.  p.  526 :  1883. 


296  LECTUEE    XIX. 

veins  of  the  abdominal  viscera  as  a  result  of  ligature  of  the 
portal  vein.  This  difficulty  has  been  overcome  by  establishing 
an  artificial  communication  between  the  portal  vein  and  the 
left  renal  vein  or  with  the  inferior  vena  cava.^  The  latter 
operation  has  been  more  especially  carried  out  by  V.  Massen 
and  J.  Pawlow  on  dogs  with  such  skill  that  several  of  the 
animals  survived  the  operation  for  mouths.  A  complete 
exclusion  of  the  liver  from  the  circulation  was  not  however 
effected,  since  the  hepatic  veins  remained  open,  and  since,  even 
after  ligature  of  the  hepatic  artery,  blood  could  reach  the  liver 
by  collateral  anastomoses.  In  animals  which  had  undergone 
this  operation  the  ammonia  of  the  urine  was  found  to  be 
increased  to  as  much  as  0.85  grm.  in  the  twenty-four  hours. 
The  great  bulk  of  the  nitrogen,  however,  was  still  secreted  as 
urea.  In  normal  dogs  the  proportion  of  ammonia  to  urea  was 
found  to  vary  between  J^  and  yL  •  in  the  operated  dogs  between 
1  and  J^.2 

Massen  and  Pawlow  also  attempted  to  extirpate  the  liver 
after  establishing  the  venous  fistula  and  tying  the  hepatic 
artery.  As  much  as  seven-eighths  of  the  liver  could  be  de- 
stroyed in  this  way,  but  the  dogs  never  survived  this  operation 
more  than  six  hours,  and  generally  only  two  or  three  hours. 

In  our  previous  remarks  on  the  precursors  of  urea  no  notice 
has  been  taken  of  a  proteid  product  of  decomposition  which  is 
very  rich  in  nitrogen,  i.  e.,  creatin.  And  yet  creatin  is  im- 
portant, as  no  other  nitrogenous  end-product  of  metabolism 
occurs  in  so  large  a  quantity  in  the  body.  Only  very  small 
quantities  of  urea  (of  which  from  30  to  40  grms.  pass  daily  into 
the  urine)  are  at  all  times  found  in  the  body.  The  total  blood 
contains  at  most  2  grms.,  and  it  could  not  be  detected  in  muscle. 
On  the  other  hand,  creatin,  of  which  only  from  0.5  to  2.5  grms. 
per  diem  pass  as  such  or  as  Creatinin  into  the  urine,  is  found 
in  the  muscles  alone  to  the  extent  of  about  90  grms.  This  fact 
renders  it  probable  that  creatin  is  converted  into  urea  and  thus 
passes  into  the  urine.  This  view  has  been  held  by  many 
physiologists,  but  the  following  observation  seemed  opposed  to 
it.  It  was  found  that  creatin,  introduced  into  an  animal, 
reappears  in  the  urine  either  unaltered  or,  consequent  upon  the 

^  N.  V.  Eck,  Travaux  de  la  Soc.  des  Naturalistes  de  St.  Petersbourg,  vol.  x.: 
1879.  Bulletins  de  la  Section  Zoologique.  Stolnikow,  Pflüger's  Arch.,  vol.  xxviii. 
p.  266  :  1882 ;  Stern,  Arch.f.  Path.  u.  Pharm.,vo\.  xix.  p.  45  :  1885 ;  W.  v.  Schröder, 
ibid.,  vol.  xix.  p.  373 :  1885 ;  Hahn,  Massen,  Nencki  et  Pawlow,  Arch.  d.  Sc.  bioL, 
vol.  i.  p.  401 :  St.  Petersburg,  1892. 

^Hahn  and  Nencki,  Arch.  d.  Sc.  biol.,  vol.  i.  pp.  461-465:  St.  Petersburg, 
1892. 


CKEATIN  297 

loss  of  one  molecule  of  water,  as  Creatinin.^  Hence  it  was 
inferred  that  creatin  could  not  be  one  of  the  antecedents  of 
urea.  But  this  inference  is  incorrect ;  because  the  creatin 
introduced  into  the  stomach  or  direct  into  the  blood  remains 
unaltered,  it  does  not  follow  that  the  creatin  formed  in  the 
muscles  behaves  in  the  same  way.  It  is  quite  impossible  for  us 
artificially  to  introduce  substances  to  the  part  where  they  would 
be  decomposed  in  health.  The  muscular  fibers  withdraw  from 
the  blood  nutritive  substances  only,  and  throw  off  the  end 
products  in  an  opposite  direction.  It  is  therefore  even  ä  priori 
unlikely  that  creatin,  when  artificially  introduced,  would  enter 
the  muscle  and  be  decomposed.  It  must  be  noted  that  it  is 
not  only  possible,  but  probable,  that  the  large  amount  of 
creatin  formed  in  muscle  becomes  further  split  up  and, 
when  converted  into  urea,  given  off  to  the  blood.  It  is  true 
that  urea  cannot  be  detected  in  muscle.  Liebig,  in  his 
celebrated  work  on  meat,  says,  "  I  think  that  I  should  be  able 
to  detect  urea  in  meat-juice  if  only  one-millionth  part  were 
present."  ^  But  it  does  not  therefore  follow  that  urea  is  not 
formed  there.  It  is  quite  possible  that  it  is  formed  in  the 
muscle,  but  that  it  is  immediately  carried  off  into  the  blood- 
current. 

I  have  already  given  the  reasons  for  my  view  that  the 
compounds  into  which  the  bulk  of  the  nitrogen  in  the  proteid 
molecule  splits  up  are  very  poor  in  carbon.  Creatin  answers  to 
this  description  ;  it  contains  only  four  atoms  of  carbon  to  three 
of  nitrogen. 

The  composition  of  creatin  has  been  thoroughly  known 
since  Volhard  and  Strecker  succeeded  in  producing  it  syn- 
thetically. Volhard^  heated  an  alkaline  solution  of  sarcosin 
(methylglycocol)  and  cyanamid  to  100°  C.  for  a  few  hours  in 
a  closed  vessel.  On  cooling,  creatin  crystallized  out.  Strecker 
went  still  more  simply  to  work.  If  he  allowed  a  saturated 
watery  solution  of  sarcosin,  with  the  requisite  amount  of 
cyanamid  and  a  few  drops  of  ammonia,  to  stand  in  the  cold,  a 
large  quantity  of  creatin  was  obtained.* 

The  constitution  of  creatin  may  be  more  readily  understood 
from  a  comparison  of  the  composition  of  guanidin,  which  is 

^G.  Meissner,  Zeitschr.  f.  rat.  3Ied.,  vol.  xxiv.  p.  100:  1865;  vol.  xxvi.  p. 
225 :  1866 ;  vol.  xxxi.  p.  283  :  1868 ;  C.  Voit,  Zeitschr.  f.  Biolog.,  vol.  iv.  p.  Ill : 
1868. 

2  Liebig,  Ann.  d.  Chem.  u.  Pharm.,  vol.  Ixii.  p.  368:  1847. 

^  Volhard,  Sitztmgsber.  d.  Munch.  Akad.,  vol.  ii.  p.  472  :  1868 ;  or  Zeitschr.  f. 
Chem.,  p.  318 :  1869. 

*  Strecker,  Jahresber.  über  Fortschr.  d.  Chem.,  note  to  p.  686  :  1868.  Vide 
also  Horbaczewski,  Wien.  med.  Jahrb.,  p.  459 :  1885. 


298 


LECTURE    XIX 


quite  analogous  to  creatin  both  in  synthesis  and  in  decomposi- 
tion.    Creatin  is  a  substituted  guanidin. 

=   C  =  NH 

Guanidin. 

\     /CH, 

^CHa  — COOH 

Creatin. 


C  =  N 

+ 

l(— H 

Cyanamid. 

+ 

/CH3 
N  — H 

\CH,- 

-COOH 

Cyanamid. 


Sarcosin. 


The  analysis  corresponds  to  the  synthesis.  On  boiling  with 
baryta  water,  the  guanidin  again  splits  into  ammonia  and  cyan- 
amid. But  the  cyanamid  takes  up  one  molecule  of  water 
and  passes  into  urea.  In  the  same  way  creatin  breaks  up  into 
urea  and  sarcosin,  a  substituted  ammonia.  The  close  affinity 
of  creatin  to  urea,  and  the  possibility  of  its  conversion  into  the 
latter,  is  thus  amply  proved. 

Creatin  is  a  neutral  compound.  By  elimination  of  one 
molecule  of  water  it  passes  into  a  strong  base — creatin. 
This  conversion  is  readily  effected  in  an  acid  solution  ;  creatin 
is  as  readily  reformed  by  an  alkaline  solution.  In  conformity 
with  this,  the  small  amount  of  creatin  daily  excreted  through 
the  kidneys  occurs  chiefly  as  Creatinin  in  acid  urine,  and  as 
creatin  in  alkaline  urine.^ 

DrechseP  has  prepared  a  base  homologous  with  creatin 
(C^H^NgO)  by  the  hydrolytic  decomposition  of  various  proteids, 
such  as  casein,  conglutin,  and  gelatin.  This  body,  which  he 
called  lysatin,  has  since  been  shown  to  be  a  mixture  of  lysin  and 
arginin ;  and  it  is  the  latter  body  which  belongs  to  the  creatin 
group  and  like  creatin  yields  urea  on  decomposition  with 
baryta  water. 

As  creatin  breaks  up  into  urea  and  methyl-amido-acetic  acid, 
so  arginin,  on  hydrolysis,  yields  urea  and  diamido- valerianic 
acid  (Ornithin).  Drechsel  reckons  that  ^  of  the  total  urea  pro- 
duced in  our  bodies  by  the  decomposition  of  proteid  may  arise 
in  this  way  by  simple  hydrolytic  dissociation.  We  see  therefore 
that  some  at  any  rate  of  the  urea  can  be  formed  independently 
of  the  processes  of  oxidation  and  subsequent  synthesis. 


1  Voit,  Zeitschr.  f.  Biolog.,  vol.  iv.  p.  115 :  1868. 

2  Drechsel,  Ber.  d.  deut.  chem.  Ges.,  vol.  xxiii.  p.  3096 :  1890. 


LECTUEE  XX 

THE   NITROGENOUS  END-PRODUCTS   OF  METABOLISM  [continued) 
URIC    ACID    AND    THE    XANTHIN    GROUP 

Uric  acid  is  the  only  nitrogenous  end-product  leaving  the 
body  in  any  quantity  that  remains  for  our  discussion. 

The  amount  of  uric  acid  excreted  in  twenty-four  hours 
varies  greatly  in  the  case  of  human  beings.  It  depends  upon 
the  nature  of  the  food.  With  a  purely  vegetable  diet  it 
amounts  from  0.2  to  0.7  grm.,  and  with  a  full  meat  diet  it  rises 
to  2  grms.  and  more.  These  differences  cannot  be  explained 
merely  by  the  varying  amount  of  proteid  in  the  food,  for  the 
proportion  of  uric  acid  to  urea  and  to  the  total  amount  of 
nitrogen  varies  greatly.  For  instance,  I  found  that  the  pro- 
portion of  urea  to  uric  acid  in  twenty-four  hours  in  the  urine  of 
a  healthy  young  man,  when  eating  nothing  but  bread,  =  f -^f 
=  82  ;  and  when  living  on  meat,  =  -y-|  =  48.  Uric  acid  is 
sometimes  entirely  absent  from  the  urine  of  carnivorous  ani- 
mals, such  as  cats  and  dogs,  and  only  a  trace  is  generally 
found  in  the  urine  of  herbivora.  The  bulk  of  the  nitrogen 
however  appears  in  this  form  in  the  urine  of  birds  and  reptiles. 

Uric  acid  has  the  composition  C^II^N^Og.  One  of  the  four 
hydrogen  atoms  is  easily  replaced  by  metals.  If  the  uric  acid 
be  dissolved  in  a  solution  of  sodium  carbonate,  the  compound 
CgllgNaN^Og  is  obtained.  This  compound  is  termed  an  acid 
urate.  On  dissolving  in  free  alkalies,  a  second  hydrogen  atom 
is  replaced  by  the  alkaline  metal.  This  compound  is  called  a 
neutral  urate.  It  is  not  known  whether  it  occurs  in  the  ani- 
mal body. 

Uric  acid  and  all  its  '  acid  salts '  are  with  difficulty  soluble 
in  water.  It  is  important,  from  a  physiological  and  pathological 
point  of  view,  to  be  accurately  acquainted  with  its  various 
degrees  of  solubility.  It  is  well  known  that  in  disease,  uric 
acid  and  urates  may  be  precipitated  from  the  fluids  of  the  body, 
and  become  deposited  in  the  joints  and  other  organs  and  tissues, 
or  from  the  urine  in  the  tubules  and  pelvis  of  the  kidney  and 
in  the  bladder.     The  painful  symptoms  of  what  are  known  as 

299 


300  LECTURE    XX 

the  uric  acid  diathesis  and  of  gout  are  due  to  this.  It  is  there- 
fore highly  interesting  to  know  under  what  conditions  uric  acid 
is  soluble,  and  under  what  circumstances  it  is  precipitated. 

A  gramme  of  free  uric  acid  requires  for  its  solution,  at  the 
temperature  of  the  room,  about  14  liters  of  water ;  at  boiling 
heat,  nearly  2  liters ;  and  at  the  temperature  of  the  body,  from 
7  to  8  liters.^  The  acid  sodium  urate  dissolves  in  1100  parts 
of  cold  and  124  of  boiling  water.  The  ammonia  salt  and  the 
salts  of  the  alkaline  earths  are  much  less  soluble. 

Sometimes  as  much  as  2  grms.  of  uric  acid  are  entirely 
dissolved  in  the  normal  urine,  the  volume  of  which  in  twenty- 
four  hours  ordinarily  amounts  to  from  1500  to  2000  corns.  It 
cannot  be  dissolved  as  a  free  acid,  for,  as  we  have  just  seen,  2 
grms.  of  free  uric  acid  require  15  liters  of  water  at  the  tem- 
perature of  the  body,  or  ten  times  more  than  actually  suffices 
for  its  solution.  We  must  therefore  assume  that  the  uric  acid 
is  dissolved  as  an  alkaline  salt.  But  this  is  apparently  opposed 
to  the  following  fact :  if  clear  acid  urine  be  allowed  to  cool  to 
the  temperature  of  the  room,  the  greater  part  of  the  uric  acid 
usually  separates  out  as  a  free  acid  in  large  and  beautiful 
crystals,  which  are  colored  brown  by  the  coloring  matter 
brought  down  with  it.  The  weight  of  the  crystals  obtained 
from  the  normal  urine  of  twenty-four  hours  may  amount  to  as 
much  as  1  grm.  How  is  this  to  be  explained  ?  If  2  liters  of 
uric  acid  solution,  saturated  at  the  temperature  of  the  body,  be 
allowed  to  cool,  only  about  1  decigrm.  of  uric  acid  is  precipi- 
tated.    How  then  can  it  reach  ten  times  that  amount  ? 

The  explanation  is  as  follows  :  If,  at  the  temperature  of 
the  body,  a  saturated  solution  of  acid  urate  of  soda,  with  a 
neutral  reaction,  be  mixed  with  a  solution  of  acid  phosphate  of 
soda  (NaH2P0^),  with  an  acid  reaction,  the  mixture  will  be 
acid.  But  if  it  be  left  to  cool  at  the  temperature  of  the  room, 
the  reaction  becomes  alkaline,  and  free  uric  acid  crystallizes  out. 
The  mass-influence  of  the  uric  acid  is  diminished  by  cooling, 
because  fewer  of  its  molecules  are  dissolved  in  the  unit  of  space. 
The  mass-influence  of  the  phosphoric  acid  becomes  relatively 
stronger.  This  acid  therefore  takes  possession  of  the  sodium 
of  the  uric  acid,  and  passes  into  the  alkaline  salt  NagHPO^.  If 
the  solution  be  heated  afresh,  the  uric  acid  crystals  redissolve, 
and  the  solution  now  gives  an  acid  reaction.  The  uric  acid  in 
acid  urine,  which  is  always  rich  in  phosphates  of  the  alkalies, 

*  As  no  account,  so  far  as  I  know,  has  ever  been  given  of  the  solubility  of 
uric  acid  at  the  temperature  of  the  body,  I  have  made  two  determinations,  vary- 
ing between  35°  and  40°  C:  1  grm.  of  uric  acid  required  7680  c.cma.  of  water  in 
the  first  experiment,  in  the  second  7320  c.cms.,  for  solution. 


UEIC   ACID  301 

behaves  in  exactly  the  same  way.  It  can  be  proved  that,  on 
cooling  the  3,cid  urine,  the  acidity  decreases  in  proportion  as 
the  uric  acid  crystallizes  out.  When  raised  to  the  temperature 
of  the  body,  the  crystals  redissolve.^ 

The  phosphates  of  the  alkalies  thus  play  the  same  part  in 
the  solution  of  the  uric  acid  that  they  do  in  the  absorption  of 
the  carbonic  acid  in  the  blood  and  in  the  tissues  (pp.  263-265). 

It  is  doubtful  whether  the  solution  and  elimination  of  the 
uric  acid  is  to  be  thus  explained  in  all  cases.  The  acidity  of 
the  urine  is  occasionally  found  to  be  increased  after  the  pre- 
cipitation of  uric  acid.^  It  is  possible  that  acids  split  off  from 
neutral  compounds  by  fermentation,  or  that  dibasic  arise  from 
monobasic  acids  by  decomposition.  This  process  may  at  times 
be  completed  even  within  the  urinary  passages,  the  consequence 
being  that  uric  acid  is  precipitated.  We  are  as  yet  far  from 
having  obtained  a  satisfactory  explanation  of  the  manner  in 
which  the  solution  of  uric  acid  is  effected. 

If  the  urine  be  only  feebly  acid  or  alkaline,  as  it  is  fre- 
quently with  a  vegetable  or  mixed  diet,  no  free  uric  acid  will 
be  deposited  on  cooling ;  but  if  the  urine  be  concentrated,  acid 
urate  of  soda  will  be  precipitated.  This  appears  in  exceedingly 
fine  round  granules  which,  like  the  free  uric  acid,  are  brown 
or  red-brown,  owing  to  the  coloring  matter  brought  down 
with  them ;  this  is  found  at  the  bottom  of  the  vessel,  and  con- 
stitutes what  is  known  as  the  lateritious  deposit. 

The  uric  acid  sediment  was  formerly  employed  as  a  guide 
in  diagnosing  disease,  but  was  very  misleading.  For  instance, 
it  was  incorrectly  assumed  that  an  increase  of  sediment  meant 
an  increase  of  uric  acid  secretion.  We  have  seen  that  the 
precipitation  of  uric  acid  depends  not  only  on  its  absolute 
amount,  but  also  on  the  concentration  and  acidity  of  the 
urine.^  It  appears  however  to  depend  on  other  conditions  as 
well.  It  is  often  found  that  urines  which  deposit  crystalline 
uric  acid  are  neither  richer  in  uric  acid  nor  more  concentrated ; 
nor  do  they  contain  more  free  acid  than  others  which  remain 
clear  or  deposit  urates.^ 

It  is  conceivable  that  uric  acid  circulates  in  the  fluids  of 
the  body  as  a  readily  soluble  compound  with  an  organic 
substance,  which  appears  in  the  urine,  and  is  then  split  up 

^Vide  Voitand  Hofmann,  "  Ueber  das  Zustandekommen  der  Harnsäuresedi- 
mente,"  Sitzungsber.  d.  bayr.  Akad.,  vol.  xi.  p.  279 :  1867.  I  have  confirmed 
Voit  and  Hofmann's  account  by  numerous  experiments. 

2  Bartels,  Deutsch.  Arch.  f.  Min.  Med.,  vol.  i.  p.  24:  1866. 

^  Compare  Botho  Scheube,  Arch.  f.  Heilkunde,  vol.  xvi.  p.  185 :  1876. 

■*  Bartels,  loc.  cit.,  p.  28. 


302  LECTUEE    XX 

by  a  fermentative  process.  If  this  happens  in  the  organs  or 
within  the  urinary  passages,  gouty  concretions  and  vesical 
calculi  are  formed.  At  any  rate,  no  increased  formation  of 
uric  acid  has  hitherto  been  found  in  gout  and  in  the  uric  acid 
diathesis.  There  is  even  less  uric  acid  eliminated  during  an 
attack  of  gout.' 

Besides,  there  is  the  important  fact  that  a  large  amount  of 
hydrochloric  acid  is  necessary^  in  order  to  separate  the  uric 
acid  from  the  urine  for  quantitative  analysis,  and  that  even 
then  it  separates  very  slowly  and  incompletely,  and  sometimes 
not  at  all,  in  spite  of  its  being  present  in  abundance.^  This 
fact  likewise  argues  that,  at  any  rate,  not  all  the  uric  acid  is 
simply  dissolved  in  the  urine  as  a  salt. 

The  chemical  constitution  of  uric  acid  has  been  the  subject 
of  investigation  by  a  large  number  of  eminent  chemists,*  and 
its  synthesis  has  been  successfully  accomplished. 

Among  the  numerous  modes  of  decomposition  of  uric  acid, 
which  have  been  accurately  studied,  the  following  is  of  peculiar 
physiological  interest,  because  the  products  obtained  play  an 
important  part  in  the  animal  economy. 

Strecker  ^  showed  that  uric  acid,  when  heated  with  concen- 
trated hydrochloric  acid  in  a  closed  tube  to  170°  C,  splits  up, 
with  hydration,  into  glycocol,  carbonic  acid,  and  ammonia : 

CsH.NA  4-  SHijO  =  CH2(NH2)COOH  +  SCOj  +  3NH3. 

Strecker  thought  that  uric  acid  would,  while  taking  up  only 

'  Garrod,  "The  Nature  and  Treatment  of  Gout":  London,  1859.  An 
account  of  the  literature  on  gout  is  given  by  Ebstein  in  his  monograph,  "Die 
Natur  und  Behandlung  der  Gicht "  :  Wiesbaden,  1882. 

2  This  phenomenon  is  probably  to  be  explained  by  the  formation  of  a  soluble 
compound  of  the  uric  acid  with  urea.  The  uric  acid  can  therefore  only  be  pre- 
cipitated when  an  amount  of  hydrochloric  acid  has  been  added  equivalent  to 
that  of  the  urea.  Compare  G.  Bunge,  Sitzungsb.  d.  Naturforsch.  Gesell,  z. 
Dorpat,  vol.  vii..  Appendix,  p.  21:  1873;  G.  Rudel,  Arch.  f.  exper.  Path.  u. 
Pharm.,  vol.  xxx.  p.  1 :  1892. 

^Salkowski,  Pfliiger's  Arch.,  to\.  v.  p.  210 :  1872;  Maly,  ibid.,  vol.  vi.  p. 
201:  1872. 

^Wöhler,  Poggendorflfs  Annal.,  vol.  xv.  p.  119:  1829;  Liebig,  ibid.,  vol. 
IV.  p.  .569  :  1829 ;  and  Ann.  d.  Chem.  u.  Pharm.,  vol.  v.  p.  288  :  1833  ;  Wöhler 
and  Liebig,  Ann.  d.  Chem.  u.  Pharm.,  vol.  xxvi.  p.  241 :  1838 ;  Adolf  Baeyer, 
ibid.,  vol.  cxxvii.  pp.  1,  199 :  1863 ;  Strecker,  ibid.,  vol.  cxlvi.  p.  142 :  1868 ;  and 
vol.  civ.  p.  177:  1870;  Kolbe,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  iii.  p.  183:  1870. 
Among  the  latest  works  on  the  constitution  of  uric  acid  may  be  mentioned  L. 
Medicus,  Ann.  d.  Chem.  u.  Pharm.,  vol.  clxxv.  p.  230 :  1875 ;  Hill,  Ber.  d. 
deutsch,  chem.  Ges.,  vol.  ix.  p.  370:  1876;  and  vol.  xi.  p.  1329:  1878;  Horbac- 
zewski,  Sitzungsber.  d.  Wien.  Akad.,  vol.  Ixxxvi.  p.  963 :  1882 ;  or  Monats- 
hefte f.  Chem.,  vol.  iii.  p.  796 :  1882 ;  and  vol.  vi.  p.  356 :  1885 ;  and  Emil 
Fischer,  Ber.  d.  deutsch,  chem.  Ges.,  vols,  i.,  xvii.  pp.  328,  1776:  1884. 

^  Strecker,  Liebig's  Annal.,  vol.  cxlvi.  p.  142  :  1868. 


URIC   ACID  303 

two  molecules  of  water,  break  up  first  into  glycocol  and  three 
molecules  of  cyanic  acid : 

CsH^N.Oa  -f  2HjO  =  CH2(NHj,)C00H  +  3C0NH. 

It  is  well  known  that  cyanic  acid,  on  coming  in  contact  with 
water,  is  at  once  converted  into  carbonic  acid  and  ammonia. 
I  may  remind  my  readers  that  the  watery  solution  of  cyanate 
of  potash  effervesces  with  acids  like  a  carbonate. 

Strecker  therefore  regarded  uric  acid  as  a  compound 
analogous  to  hippuric  acid.  As  hippuric  acid  is  a  glycocol 
conjugated  with  benzoic  acid,  so  uric  acid  is  a  glycocol  conju- 
gated with  cyanic  acid. 

The  synthesis  of  uric  acid,  which  Horbaczewski  ^  successfully 
accomplished  in  E.  Ludwig' s  laboratory  in  Vienna,  exactly  cor- 
responds to  the  decomposition  observed  by  Strecker.  Horbac- 
zewski obtained  uric  acid  by  melting  glycocol  and  urea  together 
at  from  200°  to  230°  C.  It  is  well  known  that,  on  heating 
urea,  ammonia  volatilizes  and  cyanic  acid  is  formed : — 

C<  =  O  —  NH3  =  CONH. 

Thus  if  urea  be  melted  with  glycocol,  nascent  cyanic  acid  is 
allowed  to  act  on  the  glycocol ;  one  decomposition  product  of 
the  uric  acid  in  a  nascent  state  acts  upon  the  other.  This  might 
ä  priori  be  expected  to  develop  uric  acid. 

The  following  physiological  fact  observed  by  Wöhler  ap- 
pears to  harmonize  with  these  results  of  decomposition  and 
synthesis.  Wöhler  ^  found  uric  acid,  but  no  hippuric  acid,  in 
the  urine  of  sucking  calves,  so  long  as  they  consumed  nothing 
but  milk.  But  as  soon  as  they  passed  on  to  vegetable  food,  the 
uric  acid  disappeared,  and  hippuric  acid  was  substituted. 

It  thus  appears  that  the  benzoic  acid  arising  from  vegetable 
diet  seizes  upon  the  glycocol  and  prevents  the  synthesis  of  uric 
acid. 

If  this  interpretation  be  correct,  we  should  expect,  by  the 
addition  of  aromatic  compounds,  to  be  able  to  prevent  the 
formation  of  uric  acid  in  human  beings  as  well.  This  might 
even  be  of  a  therapeutic  advantage  in  the  treatment  of  gout. 
It  is  useless  merely  to  give  benzoate  of  sodium,  as  I  have 
proved  by  many  experiments.     But  here  again  it  should  not 

1  Horbaczewski,  Sitzungsber.  d.  Wien.  Akad.,  vol.  Ixxxvi.  p.  963 :  1882 ;  or 
Monatshefte  f.  Chem.,  vol.  iii.  p.  796:  1882  ;  and  vol.  vi.  p.  356:  1885. 

2  Wöhler,  Nachr.  d.  k.  Ges.  d.  Wissensch.  zu  Göttingen,  vol.  v.  pp.  61-64 :  1849. 


304  LECTURE   XX 

be  forgotten  that  it  is  not  in  our  power  to  make  the  benzoic 
acid  reach  the  proper  point  at  the  proper  moment  when  the 
glycocol,  before  its  union  with  the  cyanic  acid,  could  react  with 
it.  As  already  mentioned,  the  benzoic  acid  in  vegetable  food  is 
not  generally  contained  as  such,  but  is  formed  in  the  body 
by  the  decomposition  and  oxidation  of  more  complex  com- 
binations. It  is  quite  possible  that  these  latter  are  taken  up 
by  the  cells  in  which  glycocol  occurs,  while  the  benzoic 
acid  already  formed  is  rejected.  At  any  rate,  it  must  be 
remembered  that  to  prevent  the  formation  of  uric  acid  in 
gout  would  only  affect  the  symptoms.  It  is  impossible  to 
treat  the  essential  cause  of  the  disease,  because  it  is  quite 
unknown  to  us. 

With  a  view  to  obtaining  further  insight  into  the  constitu- 
tion of  uric  acid,  the  products  of  its  simultaneous  decomposi- 
tion and  oxidation  have  been  investigated — products  obtained 
by  the  action  of  oxidizing  agents.  These  products  are  like- 
wise of  great  interest,  because  among  them  compounds  occur 
which  are  also  met  with  in  the  metabolism  of  the  animal 
body. 

A  solution  of  permanganate  of  potash  causes  uric  acid  to 
break  up,  even  in  the  cold,  into  allantoin  and  carbonic  acid :  ^ 
C,H,NP3  -F  O  +  HP  =  C,H,NP3  +  CO,. 

Allantoin  was  discovered  by  Vauquelin^  in  the  allantoic 
fluid  of  the  cow,  was  subsequently  found  by  Wöhler  ^  in  calves' 
urine  as  well,  and  was  further  investigated  both  by  him  and 
by  Liebig.*  Later  this  compound  was  also  detected  in  the 
allantoic  fluid  and  in  the  urine  of  new-born  children,  and  oc- 
casionally in  dogs'  urine.^ 

The  further  action  of  oxidizing  agents  upon  allantoin  ^  pro- 
duces urea  and  oxalic  acid,  and  the  latter  ultimately,  under  the 
same  influence,  yields  carbonic  acid. 

If  nitric  acid  be  employed  for  the  purpose  of  splitting  up 
and  oxidizing  uric  acid,  urea  and  carbonic  acid  are  again 
obtained  as  end-products.  Compounds  occur  as  intermediary 
products  which,  although  they  do  not  appear  in  the  animal 

^  Claus,  Ber.  d.  deutsch,  ehem.  Ges.  d.  Wissensch.  zu  Göttingen,  vol.  v.  pp. 
61-64:  1849. 

^Buniva  et  Vauquelin,  Ann.  de  Chim.,  vol.  xxxiii.  p.  269,  ann.  viii«. :  1799. 
Vide  also  Lassaigne,  Ann.  de  Chim.  et  de  Phys.,  vol.  xvii.  p.  301 :  1821. 

^  Wöhler,  Nachr.  d.  k.  Ges.  d.  Wissensch.  zu  Göttingen,  p.  61 :  1849. 

^  Wöhler  and  Liebig,  Ann.  d.  Chem.  u.  Pharm.,  vol.  xxvi.  p.  244 :  1838. 

^  E.  Salkowski,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  ix.  p.  719 :  1876 ;  and  vol. 
xi.  p.  500:  1878. 

Ö  For  the  synthesis  and  composition  of  allantoin,  vide  Grimaux,  Compt.  rend. 
vol.  Ixxxiii.  p.  62 :  1876. 


UEIC  ACID  305 

body,  are  of  interest  in  so  far  as  they  help  to  throw  some  light 
upon  the  consstitution  of  uric  acid.  Alloxan  and  urea  are  the 
first  compounds  formed  by  the  nitric  acid  in  the  presence  of 
cold : 

O— NH       NH, 


C5H4N  A  +  O  +  H2O  =  CO    Co  +  c  =  o 

Uric  acid.  io-NH        NH, 

Alloxan.        Urea. 


Alloxan,  when  heated  with  nitric  acid,  passes  into  parabanic 
and  carbonic  acids : 


CO— NH  CO— NH 

CO    CO  +  O  =  CO2  +  CO 

CO— NH  CO— NH 

Alloxan.         Parabanic  acid,  or  Oxalylurea 


The  parabanic  acid,  with  hydration,  passes  into  oxaluric 
acid : 

CO— NH  CONHCONHj 

>C0  =  0  +  H20=  I  ' 

CO-iH  COOH 

Parabanic  acid.  Oxaluric  acid. 


The  latter,  by  taking  up  a  second  molecule  of  water,  breaks 
up  into  oxalic  acid  and  urea  : 

CONHCONH2  COOH     /NH2 

+  H,0=  +<C0 

COOH  ^     '        COOH     X^Ha 

Oxaluric  acid.  Oxalic  acid.     Urea. 


Oxaluric  acid  occurs  in  the  human  urine  ^  in  minute 
quantities. 

The  following  formula,  which  was  composed  by  Medicus  ^ 
and  confirmed  by  Emil  Fischer^  from  extensive  observations, 

■I  Ed.  Schunck,  Proceed.  Roy.  Soc,  vol.  xvi.  p.  140:  1868;  C.  Neubauer, 
Zeitschr.  f.  anal.  Chem.,  vol.  vii.  p.  225  :  1868. 

2  Medicus,  Ann.  d.  Chem.  u.  Pharm.,  vol.  clxxv.  p.  230  :  1875. 

^  Fischer,  Ber.  d.  deutsch,  chem.  Ges.,  vol.  xvii.  pp.  328,  1776  :  1884. 

20 


306  LECTURE   XX 

agrees    with    all   the    decompositions   of    uric    acid   we   have 
described : 


HN— C NH 


Another  synthesis  of  uric  acid/  also  discovered  by  Horbac- 
zewski,  agrees  well  with  this  structural  formula.  He  found  it 
could  be  synthesized  by  fusing  together  trichlorlactic  acid  and 
urea. 

As  we  have  seen  that  uric  acid  is  transmuted  into  urea  and 
carbonic  acid  by  oxidizing  agents  outside  the  organism,  we 
should  expect  to  find  the  same  process  going  on  within  the 
organism,  and  that  uric  acid  is  one  of  the  antecedents  of  urea. 
If  uric  acid  be  introduced  into  the  organism  of  a  dog,  it  cer- 
tainly becomes  almost  entirely  changed  into  urea,^  But  it  by 
no  means  follows  that  part  of  the  urea  normally  formed  arises 
from  uric  acid.  This  idea  is  frequently  met  with,  and  especially 
in  pathological  literature.  It  was  thought  that,  in  disturbances 
of  external  and  internal  respiration  (such  as  affections  of  the 
lungs,  anemia,  etc.),  an  increase  takes  place  in  the  elimination 
of  uric  acid  as  a  product  of  incomplete  combustion.  This 
supposition  has  not,  however,  been  confirmed.  Senator '  could 
detect  no  increase  in  the  excretion  of  uric  acid  in  dogs,  cats, 
and  rabbits  when  respiratory  disturbances  were  artificially  in- 
duced ;  nor  could  Naunyn  and  Riess  *  do  so  after  venesections. 
Moreover  the  numerous  accounts  given  of  the  increased  elimina- 
tion of  uric  acid  in  human  beings  in  consequence  of  respiratory 
disturbances,  do  not  rest  on  exact  observation.  In  the  first 
place,  investigators  fell  into  the  error,  already  alluded  to,  of 
inferring  an  increase  of  uric  acid  from  an  increase  of  sediment ; 
and  in  the  second  place,  they  did  not  sufficiently  take  into  con- 
sideration how  much  the  formation  of  uric  acid  depends  upon 
diet.  It  should  be  especially  noted  that  a  fasting,  and  particu- 
larly a  febrile  person — in  whom  it  is  well  known  that  the  pro- 

1  J.  Horbaczewski,  Monatshefte  für  Chemie,  vol.  viii.  pp.  201,  584:  1887. 

^Zabelin,  Liebig's  Annal.  d.  Chem.  u.  Pharm.,  SuppL,  vol.  ii.  p.  326:  1862 
and  1863.  The  views  of  earlier  authors  on  the  conversion  of  uric  acid  into  urea 
will  be  found  here.  [It  has  been  shown  recently  by  Minkowski  that  a  consider- 
able amount  of  the  uric  acid  is  converted  in  the  organism  of  the  dog  into  allan- 
toin,  in  which  form  it  is  excreted  in  the  urine.  Minkowski,  Arch.  f.  exper.  Path. 
u.  Pharm.,  vol.  xli.  p.  375 :  1898.] 

^Senator,  Virchow's  Arch.,  vol.  xlii.  p.  35:  1868. 

*  B.  Naunyn  and  L.  Riess,  Du  Bois'  Arch.,  p.  381 :  1869. 


URIC   ACID  307 

teid-decomposition  is  increased — behaves  exactly  like  a  person 
who  lives  on  meat.  The  results  of  all  calculations  bearing  upon 
the  elimination  of  uric  acid  in  respiratory  disturbances,  and 
concerning  the  relation  of  uric  acid  to  urea  in  these  affections, 
vary  within  the  same  limits  as  they  do  in  the  case  of  healthy 
people. 

Increased  excretion  of  uric  acid  has  hitherto  been  proved 
only  in  the  case  of  one  disease,  leukemia.  Bartels^  recounts 
that  he  found  4.2  grms.  of  uric  acid  in  the  urine  of  a  leukemic 
patient  during  twenty-four  hours,  of  which  1.8  grm.  had  crys- 
tallized out.  O.  Schultzen^  even  found,  in  the  urine  of  a  case 
of  leukemia  during  twenty-four  hours,  a  sediment  consisting  of 
4.5  grms.  of  free  uric  acid  and  1.45  grm.  of  urate  of  ammonia. 
Such  large  amounts  have  never  been  observed  in  healthy 
people.  In  the  cases  of  leukemia  where  the  amount  of  uric 
acid  does  not  exceed  that  of  healthy  people,  the  proportion  of 
uric  acid  to  urea  is  increased,  frequently  in  the  proportion  of 
only  12  grms.  of  the  latter  to  1  grm.  of  uric  acid.^  Fleischer 
and  Penzoldt"'  have  made  a  careful  investigation  on  this  subject. 
They  dieted  a  leukemic  patient  and  a  person  in  good  health  in 
precisely  the  same  way  ;  they  both  excreted  the  same  amount  of 
urea,  but  the  leukemic  patient  eliminated  daily  an  average  of 
1.29  grm.  of  uric  acid,  while  that  eliminated  by  the  healthy 
person  amounted  to  0.66  grm.,  or  half  as  much.  Careful  exper- 
iments carried  out  by  Stadthagen^  in  Kossel's  laboratory  led  to 
similar  results. 

This  occurrence  cannot,  for  the  reasons  already  given,  be 
referred  to  a  diminution  of  oxygen  in  consequence  of  the  de- 
crease in  red  blood-corpuscles.  It  was  therefore  thought  that 
the  cause  was  to  be  sought  in  the  enlargement  of  the  spleen 
and  in  the  increase  of  leucocytes.  Uric  acid  is  constantly 
found  in  the  spleen,  which  has  given  rise  to  the  idea  that  it 
is  chiefly  formed  here.  Enlargement  of  the  spleen,  however, 
occurs  in  other  diseases,  in  intermittent  fever  and  in  typhoid, 
without  any  increase  of  uric  acid  that  could  be  detected.^  Nor 
could  Stadthagen  confirm  the  view  that  uric  acid  occurred  in 
the  spleen ;  he  could  not  detect  even  a  trace  of  it  in  the  liver 

1  Bartel's  Deutsch.  Arch.  f.  Min.  Med.,  vol.  i.  p.  23 :  1866. 

2  Steinberg,  "  über  Leukämie,"  Inaug.  Dissert.:  Berlin,  1868. 

*H.  Ranke,  "Beobachtungen  und  Versuche  über  die  Ausscheidung  der 
Harnsäure,"  p.  27:  München,  1858;  and  Salkowski,  Virchow's  Arch.,  vol.  1.  p. 
1'74 :  1870 ;  and  vol.  lii.  p.  58  :  1871. 

■*  Fleischer  and  Penzoldt,  Deutsch.  Arch.  f.  Min.  Med.,  vol.  xxvi.  p.  368  : 
1880. 

5  Stadthagen,  Virchow's  Arch.,  vol.  cix.  p.  396  :  1887. 

«  Bartels,  Deutsch.  Arch.  f.  Min.  Med.,  vol.  i.  p.  28 :  1866. 


308  LECTURE   XX 

and  spleen  of  either  a  leukemic  patient  or  a  healthy  person. 
It  is  possible  that  uric  acid  may  be  a  product  of  the  metabolism 
of  leucocytes,  independent  organisms  which  travel  through 
our  tissues,  after  the  manner  of  '  symbionta.'  Uric  acid  has 
been  observed  to  be  the  end-product  of  tissue-change  in  all 
kinds  of  the  lower  animals.  In  this  connection  it  is  note- 
worthy that  quinine,  which  diminishes  the  ameboid  move- 
ments of  leucocytes,  also  lessens  the  elimination  of  uric 
acid.^ 

Horbaczewski  ^  confirms  Stadthagen's  statement  that  the 
spleen  contains  no  uric  acid.  In  the  fresh  splenic  pulp  of 
calves  directly  after  death  he  could  detect  no,  or  only  the 
slightest  trace  of,  uric  acid.  If,  however,  the  fresh  splenic  pulp 
were  allowed  to  stand  with  blood  at  the  temperature  of  the 
body,  considerable  quantities  of  uric  acid  were  formed,^  e.  g.,  .14 
grm.  from  100  grms.  of  splenic  pulp  in  seven  and  a  half  hours. 
This  formation  of  uric  acid  also  occurred  if,  instead  of  splenic 
pulp,  an  extract  obtained  by  boiling  the  spleen  with  normal 
salt  solution  were  used,  and  allowed  to  stand  some  hours  with 
blood  at  the  body  temperature.  In  this  process  oxygen  is 
necessary,  since  only  small  quantities  of  uric  acid  are  formed, 
if  hydrogen  be  led  through  the  mixture  of  splenic  pulp  and 
blood.  If  the  splenic  pulp  be  allowed  to  putrefy  with  water 
at  50°  C,  xanthin  and  hypoxanthin  can  be  prepared  from  the 
watery  extract.  These  bases  however,  like  the  uric  acid,  could 
not  be  found  by  Horbaczewski  pre-formed  in  the  splenic  pulp. 
Moreover  they  are  not  the  precursors  of  uric  acid  since,  as  is 
well  known,  they  are  not  converted  by  oxidation  into  uric  acid. 
We  must  assume  that  the  xanthin  bases  and  the  uric  acid  are 
formed  according  to  the  varying  conditions  under  which  the 
experiment  is  carried  out,  from  some  common  precursor.  This 
precursor  is  a  substance  derived  from  some  nuclein  compound 
of  the  nuclei  of  the  leucocytes,  and  probably  occurs  in  all  other 
tissues  which  contain  nuclein. 

The  theory  that  uric  acid  is  the  result  of  imperfect  respira- 
tion is  negatived  by  the  simple  fact  that  in  birds,  which  of  all 
animals  have  the  most  active  respiration,  the  bulk  of  the 
nitrogen  leaves  the  body  as  uric  acid.  The  nitrogen  may  be 
introduced  into  the  organism  of  the  bird  in  whatever  form  you 

^  Ranke,  loc.  cit.  This  account  has  been  amply  confirmed,  especially  by 
Prior's  thorough  investigation,  Pfliiger's  Arch.,  vol.  xxxiv.  p.  237 :  1884.  The 
■whole  literature  will  be  found  here. 

^  J.  Horbaczewski,  Sitzungsb.  d.  Akad.  d.  Wissensch.  in  Wien.,  Math.-nat. 
Kl.,  vol.  xcviii.  pt.  iii.,  July,  1889,  and  vol.  c.  pt.  iii.,  April,  1891. 

^  These  results  have  been  confirmed  by  P.  Giacosa,  Wien.  med.  Blätter,  No. 
32:  1890, 


UEIC   ACID  309 

like — as  an  amido-acid  :  leucin,  glycocol,  or  aspartic  acid  ;  ^  as 
urea ;  ^  as  carbonate  or  formate  of  ammonia  ;  ^  as  hypoxanthin  ^ 
— it  invariably  appears  in  the  urine  as  uric  acid. 

We  cannot  even  guess  in  what  way  these  nitrogenous  com- 
pounds take  part  in  the  synthesis  of  uric  acid.  For  instance, 
carbonate  of  ammonia  alone  cannot  furnish  material  for  the 
formation  of  uric  acid ;  a  further  compound,  rich  in  carbon, 
and  containing  little  or  no  nitrogen,  is  required.  Either  glyco- 
col  or  lactic  acid  would  satisfy  these  requirements,  but  nothing 
definite  is  known  on  this  point. 

It  now  only  remains  for  us  to  consider  where  the  uric  acid 
is  formed.  This  is  important  from  a  physiological  as  well  as 
from  a  pathological  point  of  view.  The  most  complete  inves- 
tigations upon  this  subject  of  recent  times  have  been  made  by 
Schröder  ^  and  Minkowski.^ 

Schröder  succeeded,  in  Ludwig's  laboratory,  in  overcoming 
the  immense  difficulties  encountered  in  the  extirpation  of  the 
kidneys  of  birds.  Hens  lived  from  five  to  ten  hours  after  their 
kidneys  had  been  either  extirpated  or  detached  from  the 
circulation  by  ligaturing  the  aorta  and  vena  cava  above  the 
kidney.  In  this  time  uric  acid  had  accumulated  in  the  organs. 
A  considerable  amount  of  uric  acid  was  obtained  from  the 
heart  and  the  lungs  together  with  the  blood  in  them,  but  none 
from  the  normal  organs,  by  the  method  adopted  by  Schröder. 
Hence  it  follows  that  the  uric  acid  is  not  produced,  or  at  any 
rate  not  exclusively  formed,  in  the  kidneys  of  fowls.  Experi- 
ments in  which  snakes'  kidneys  were  extirpated  gave  the  same 
results,  only  that  here  the  amount  of  uric  acid  that  accumulated 
was  larger,  because  snakes  survive  the  operation  for  a  much 
longer  time.  They  lived  from  five  to  nine  days  afterwards, 
and  after  death  a  large  quantity  of  uric  acid  was  found  in  all 
their  organs,  but  most  abundantly  in  the  spleen.  A  consider- 
able amount  of  uric  acid  was  obtained  from  the  blood.  Hence 
also  in  snakes  uric  acid  is  not  primarily  formed  in  the  kidneys. 

The  locality  of  the  formation  of  uric  acid  in  mammals  has 
not  been  experimentally  investigated.  At  the  same  time,  the 
existence  of  small  amounts  of  uric  acid  in  the  liver,  lungs,  and 


'  Von  Knieriem,  Zeitschr.  f.  Biolog.,  vol.  xiii.  p.  36 :  1877. 

2  Meyer  and  Jaife,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  x.  p.  1930 :  1877.  Vide 
also  Cech,  ibid.,  vol.  x.  p.  1461 :  1877. 

*  Von  Schröder,  Zeitschr.  f.  physiol.  Chem.,  vol.  ii.  p.  228:  1878. 

*"W.  von  Mach,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxiv.  p.  389  :  1888. 

5 Von  Schröder,  Du  Bois'  Arch.,  Sup.,  p.  113:  1880;  and  "Beiträge  zu 
Physiol.,  Carl  Ludwig  zu  seinem  70  Geburtstage  gewidmet  von  seinen  Schülern," 
p.  89  :  Leipzig,  1887. 

«  Minkowski,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxi.  p.  41  :  1886. 


310  LECTURE   XX 

other  organs  has  been  ascertained.^  The  occurrence  in  gout  oi 
large  quantities  of  uric  acid  in  the  joints,  tendons,  and  liga- 
ments, under  the  skin,  and  in  other  organs,  without  any 
previous  disturbance  in  the  functions  of  the  kidney,  seems  to 
show  that  uric  acid  is  not  primarily  formed  in  the  kidneys  in 
the  case  of  mammals  any  more  than  it  is  in  the  case  of  birds 
and  reptiles. 

Minkowski  ^  endeavored  to  ascertain  whether  this  process 
went  on  in  the  liver.  He  carried  out  his  experiments  on  birds. 
The  difficulties  met  with  in  mammals,  in  endeavoring  to  cut  the 
liver  out  of  the  circulation,  do  not  occur  in  birds,  and  there  is 
no  need  in  the  latter  to  guard  against  the  intense  congestion 
in  the  portal  system  by  establishing  artificial  communication. 
Fortunately,  such  a  communication  has  a  natural  existence  in 
birds.  Birds  have  a  vascular  system  in  the  kidney  similar  to 
the  portal  circulation  in  the  liver.  There  is  a  vena  advehens  in 
the  kidney  which  brings  to  that  organ  the  blood  of  the  caudal 
vein,  the  iliac  veins,  and  the  veins  leading  from  the  pelvic 
organs.  This  vena  advehens  communicates  with  the  portal 
veins  by  means  of  Jacobson's  vein.  After  tying  the  portal  vein 
therefore,  the  blood  from  the  intestine  can  pass  through  the 
kidneys  to  the  inferior  vena  cava,  and  no  stagnation  occurs.^ 
Minkowski  therefore  tried,  by  experiments  on  birds,  to  find 
out  what  influence  the  removal  of  the  liver  has  upon  the 
composition  of  urine.  He  made  his  experiments  on  geese, 
because  these  large  birds  yield  a  sufficient  amount  of  urine  for 
the  purpose  of  analysis,  and  because  they  secrete  urine  in 
abundance  after  removal  of  the  liver.  He  operated  upon  as 
many  as  sixty  geese,  and  in  most  cases,  not  only  tied  the 
hepatic  vessels,  but  also  completely  extirpated  the  liver,  except 
a  very  small  remnant  which  he  was  obliged  to  leave  in  the 
immediate  neighborhood  of  the  vena  cava,  as  in  birds  this 
latter  passes  through  the  liver.  This  remnant  was  destroyed  by 
crushing.  The  animals  thus  operated  upon  mostly  lived  for 
more  than  six  hours,  and  a  few  of  them  for  twenty  hours.  The 
large  intestine  was  tied  above  the  cloaca  in  order  to  obtain  the 
urine  in  a  pure  condition. 

The  result  obtained  was  that  the  total  nitrogen  eliminated 
after  the  extirpation  of  the  liver  was  not  greatly  diminished ; 
it   amounted    to   about    from   one-half  to   two-thirds   of  the 


^  An  account  of  the  literature  is  given  by  Schröder,  Du  Bois'  Arch.,  Sup., 
p.  143.    For  the  opposite  view  of  Stadthagen,  see  the  earlier  reference. 

^  Minkowski,  loc.  cit.,  and  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxxi.  p. 
214:  1893. 

*  Stern,  Arch.f.  exper.  Path.  u.  Pharm.,  vol.  xix.  p.  45:  1885. 


UEIC   ACID  311 

quantity  normally  excreted  by  geese  in  the  same  time.  On 
the  other  hand,  the  proportion  of  uric  acid  to  the  total  nitrogen 
in  the  urine  was  very  diiferent.  In  healthy  geese  the  nitrogen 
eliminated  as  uric  acid  amounts  to  from  60  to  70  per  cent,  of 
the  total  nitrogen ;  in  geese  after  removal  of  the  liver,  only  to 
from  3  to  6  per  cent. 

The  relative  amount  of  another  nitrogenous  constituent  of 
the  urine,  ammonia,  is  altered  in  the  reverse  direction  after 
extirpation  of  the  liver.  The  ammonia  in  the  urine  of  normal 
geese  amounts  to  from  9  to  1 8  per  cent,  of  the  total  nitrogen  ; 
that  in  the  urine  of  geese  after  extirpation  of  the  liver,  from 
50  to  60  per  cent. 

From  this  Minkowski  concludes  that  ammonia  is  a  normal 
antecedent  of  uric  acid,  and  that  the  synthetic  conversion  of 
ammonia  into  uric  acid  in  the  organism  of  birds  can  only  take 
place  if  the  liver  is  free  to  perform  its  functions.  Minkowski 
does  not  say  that  the  liver  is  the  locality  of  uric  acid  forma- 
tion. It  is  possible  that  the  functions  of  the  liver  are  only 
indirectly  called  into  play  in  the  formation  of  uric  acid  in  other 
organs. 

The  following  very  important  fact  observed  by  Minkowski 
may  be  interpreted  in  this  sense.  A  very  large  quantity  of 
lactic  acid  was  found  in  the  urine  of  geese  after  removal  of  the 
liver.  Minkowski  could  not  detect  any  lactic  acid  in  the 
normal  urine  of  geese,  whereas  after  the  operation  there  was  so 
large  a  quantity  as  to  be  equivalent  to  the  amount  of  ammonia 
excreted,  and  sufficient  to  make  the  urine  strongly  acid. 

The  extirpation  of  the  liver  is,  therefore,  in  some  way  as  yet 
inexplicable,  followed  by  the  appearance  of  large  quantities  of 
lactic  acid,  and  the  formation  of  uric  acid  being  inhibited  in 
any  organ  is  perhaps  only  indirectly  the  consequence  of  the 
occurrence  of  the  acid.  We  have  already  seen  that  acids  check 
the  formation  of  urea  and  increase  the  elimination  of  ammonia 
in  the  organism  of  mammals.  Why  may  not  acids  have  the 
same  inhibitory  effect  upon  the  formation  of  uric  acid  in  the 
organism  of  birds?  In  fact,  by  administering  sodium  car- 
bonate, Minkowski  succeeded  in  reducing  the  elimination  of 
ammonia  in  a  normal  goose  from  11  to  3  per  cent,  of  the  total 
nitrogen. 

I  will  only  add  that  in  diseases  of  the  liver,  and  especially 
in  acute  atrophy  of  the  liver,  and  in  cases  of  phosphorus 
poisoning,  large  quantities  of  lactic  acid  have  been  observed 
in  the  urine.^  May  not  the  increased  elimination  of  ammonia 
in  cirrhosis  of  the  liver  (p.  295)  be  likewise  referred  to  this 

^  Schultzen  and  Riess,  Ann.  des  Charite-Krankenhauses,  vol.  xv. :  1869. 


312  LECTUEE    XX 

fact  ?  So  far  as  my  knowledge  extends,  no  determinations  have 
ever  been  made  of  the  acidity  of,  and  the  lactic  acid  present  in, 
the  urine  of  persons  suflFering  from  cirrhosis  of  the  liver. 

1  will  also  take  this  opportunity  of  mentioning  that  the  oc- 
currence of  an  organic  acid  (oxybutyric  acid)  and  simultaneously 
an  increased  elimination  of  ammonia  has  also  been  observed  in 
cases  of  diabetes  mellitus.^ 

It  may  even  be  doubted  whether  ammonia  is  the  normal 
antecedent  of  urea  and  of  uric  acid.  It  is  possible  that  the 
nitrogen,  which  under  normal  circumstances  splits  off  from  the 
proteid  molecule  as  a  neutral  compound,  separates  as  ammonia 
under  the  influence  of  the  abnormal  acids. 

The  facts  observed  by  Minkowski  may  therefore  be  inter- 
preted in  many  different  ways.  Minkowski  himself  inclines 
to  the  idea  that  the  bulk  of  the  uric  acid  in  the  liver  is 
normally  formed  by  synthesis  from  ammonia  and  a  non- 
nitrogenous  substance,  and  imagines  this  latter  to  be  lactic 
acid.^  Minkowski  grounds  this  view  on  the  probability  of 
ammonia  and  lactic  acid  both  having  a  common  source  in 
proteid.  As  already  stated,  he  always  found  the  lactic  acid  in 
quantities  equivalent  to  the  ammonia.  It  increased  in  quantity 
with  the  amount  of  proteid  in  the  food,  and  was  independent 
of  the  addition  of  carbohydrates ;  it  increased  also  under  the 
same  condition  under  which  an  increase  of  uric  acid  normally 
takes  place. 

Of  the  numerous  facts  ascertained  by  Minkowski,  I  would 
emphasize  the  following : 

Besides  the  uric  acid  and  the  ammonia,  which  form  the 
bulk  of  the  nitrogenous  compounds  in  the  normal  urine  of 

'  Hallervorden,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xii.  p.  268:  1880; 
Stadelmann,  ibid.,  vol.  xvii.  p.  419 :  1883  ;  Minkowski,  ibid.,  vol.  xviii.  pp.  35, 
147:  1884;  Kiilz,  Zeitschr.  f.  Biolog.,  vol.  xx.  p.  165:  1884;  H.  Wolpe,  Arch.f. 
exper.  Path.  u.  Pharm.,  vol.  xxi.  p.  138 :  1886. 

2  The  lactic  acid  found  by  Minkowski  in  the  urine  of  geese  whose  livers 
had  been  removed  was  the  optically  active  sarcolactic  acid.  There  are  known  to 
be  three  isomeric  lactic  acids:  ethylene  lactic  acid  [CH2(OH)CH2COOH]  or 
hydr'acrylic  acid,  which  has  not  been  detected  in  the  animal  body,  and  the  two 
ethylidene  lactic  acids  [CH3CH(0H)C00H].  Of  the  two  last,  the  lactic  acid  of 
fermentation,  which  is  formed  by  the  fermentation  of  sugar  of  milk  in  milk,  and 
by  the  fermentation  of  the  carbohydrates  in  the  intestine,  is  optically  inactive ; 
the  other,  the  sarcolactic  acid,  is  optically  active,  as  it  rotates  the  plane  of 
polarization  to  the  right.  The  latter  is  obtained  from  muscles  (compare  Lecture 
XXIII.),  and  is  met  with  frequently  in  pathological  products :  in  urine,  in 
phosphorus-poisoning  and  atrophy  of  the  liver,  in  osteomalacia,  in  the  sweat  in 
puerperal  fever,  and  in  various  pathological  exudations.  We  owe  the  most 
minute  inquiries  into  isomeric  lactic  acids  to  J.  Wislicenus  {Ann.  d.  Chem.  u. 
Pharm.,  vol.  clxvi.  p.  3:  1873;  and  vol.  clxvii.  pp.  302,  346:  1873),  and  to  E. 
Erlenmeyer  {ibid.,  vol.  clviii.  p.  262:  1871;  and  vol.  cxci.  p.  261;  1878).  A 
summary  of  the  literature  on  isomeric  lactic  acids  is  given  in  these  works. 


XANTHIN    AND    HYPOXANTHIN  313 

birds,  there  is  always  a  small  amount  of  urea.  The  nitrogen 
eliminated  in  this  form  amounts  to  from  about  2  to  4  per 
cent,  of  the  total  nitrogen.  The  proportion  of  urea  to  the 
total  nitrogen  remained  unaltered  after  extirpation  of  the 
liver.  The  urea  in  the  urine  of  birds  is  therefore  not  formed 
in  the  liver.  But  of  course  this  does  not  justify  any  con- 
clusion with  regard  to  the  locality  of  the  formation  of  urea 
in  mammals. 

If  urea  be  artificially  introduced  into  the  organism  of 
normal  birds,  the  nitrogen  of  the  urea,  according  to  the  experi- 
ments of  Meyer  and  Jaff§  already  quoted,  reappears  as  uric 
acid  in  the  urine.  Minkowski  injected  solutions  of  urea  either 
subcutaneously  or  into  the  stomach  of  his  geese,  after  removal 
of  the  liver  ;  the  urea  reappeared  in  the  urine  unaltered.  This 
fact  also  seems  to  warrant  the  conclusion  that  uric  acid  is 
formed  by  synthesis  in  the  liver,  but  it  is  capable  of  being 
otherwise  interpreted.  I  may  express  the  hope  that  the  arti- 
ficial transmission  of  blood  through  the  excised  liver  of  birds 
may  soon  give  a  satisfactory  reply  to  this  question. 

The  facts  obtained  both  by  Meissner  *  and  by  Schröder  ^ 
agree  in  showing  that  the  amount  of  normal  uric  acid  is  always 
larger  in  the  liver  than  in  the  blood  of  birds ;  and  they  are 
moreover  in  harmony  with  the  theory  that  uric  acid,  or  at  any 
rate  a  portion  of  it,  is  formed  in  the  liver  of  birds. 

These  experiments  on  birds  do  not  permit  of  any  conclusion 
being  drawn  as  to  the  seat  of  formation  of  uric  acid  in  mam- 
mals, and  there  are  no  grounds  for  assuming  that  the  chief  part 
of  the  uric  acid  in  mammals  is  also  formed  in  the  liver.  The 
fact  that  the  excretion  of  uric  acid  is  unaltered  in  cirrhosis  of 
the  liver  is  against  such  a  view. 

In  all  the  tissues  of  our  body,  and  especially  in  the  nuclei 
of  the  cells,  there  are  small  quantities  of  two  bases  rich  in 
nitrogen,  the  empirical  formulge  of  w^hich  would  lead  to  the 
conclusion  that  they  are  closely  related  genetically  to  uric  acid. 
I  mean  xanthin  and  hypoxanthin,  or  sarcin.^  They  differ 
from  uric  acid  only  in  their  smaller  amount  of  oxygen  : 

Uric  acid CäH^N^Os 

Xanthin C5H4NA 

Hypoxanthin C5H4N4O 


'  Meissner,  Zeitschr.  f.  rat.  Med.,  vol,  xxxi.  p.  144:  1868. 

*W.  von  Schröder,  "  Beiträge  zur  Physiol.,  Carl  Ludwig  zu  seinem  70 
Geburtstage  gewidmet  von  seinen  Schülern,"  p.  98,  Leipzig  :  1887. 

^  J.  Piccard,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  vii.  pp.  1714-1719:  1874; 
Kossei,  Zeitschr.  f.  physiol.  Chem.,  vol.  vi.  p.  422:  1882;  vol.  vii.  p.  7:  1882. 


314  LECTUEE    XX 

As  yet  however  no  one  has  succeeded  in  transmuting  the  three 
compounds  into  one  another/  The  facts  that  xanthin  on  oxi- 
dation yields  alloxan  and,  when  acted  on  by  fuming  hydro- 
chloric acid,  glycocol,  seem  to  point  to  its  having  a  constitu- 
tion somewhat  analogous  to  that  of  uric  acid.^ 

But  there  is,  in  close  affinity  to  xanthin,  a  third  compound, 
GUANiN^  (CgHjNgO),  which  frequently  occurs  in  the  tissues 
together  with  xanthin  and  hypoxanthin,  and,  like  these,  is  a 
decomposition-product  of  the  nuclein  of  the  cell-nuclei.  This 
is  converted  into  xanthin  by  the  action  of  nitrous  acid. 

More  recently  Kossel^  has  discovered  a  fourth  base  rich 
in  nitrogen  as  a  constituent  of  the  nuclei ;  this  he  terms 
ADENIN.  It  has  the  composition  C^H^Ng  and  is  therefore  a  , 
polymer  of  hydrocyanic  acid,  and  is  related  to  hypoxanthin  in 
the  same  way  as  guanin  is  to  xanthin.  It  is  converted  into 
hypoxanthin  by  nitrous  acid. 

Only  a  very  small  quantity  of  xanthin  is  invariably  present 
in  human  urine ;  ^  in  rare  cases  it  may  form  vesical  calculi. 

Xanthin,  hypoxanthin,  guanin,  and  adenin,  which  are 
usually  designated  by  the  generic  name  of  xanthin  bases,  un- 
doubtedly belong  to  the  antecedents  of  urea  or  of  uric  acid.^ 
They  occur  in  too  large  a  quantity  in  the  tissues,  and  in  too 
small  a  one  in  the  urine,  for  it  to  be  possible  that  they  are 
eliminated  unchanged.  Guanin  is,  like  creatin,  a  substituted 
guanidin.  All  the  reasons  which  were  adduced  in  favor  of 
the  conversion  of  creatin  into  urea  are  equally  applicable  to 
guanin. 

The  xanthin  bases  are  however  not  merely  end-products : 
they  are  also  initial  products  of  metabolism,  since  they  form 
important  constituents  of  the  heads  of  spermatozoa.  The 
chemical  constitution  of  these  bases  acquires  therefore  consider- 
able physiological  interest.     Even  if  we  are  unable  at  present 

^  Emil  Fischer  {Ber.  d.  deutsch,  ehem.  Ges.,  vol.  xvii.  pp.  328,  329 :  1884) 
was  uiiable  to  confirm  Strecker's  account  that  uric  acid  could  be  reduced  to 
xanthin  and  hypoxanthin  by  nascent  hydrogen,  and  that  hypoxanthin  could  be 
oxidized  into  xanthin  by  nitric  acid.  Vide  also  Kossel,  Zeitschr.  f.  physiol. 
Chem.,  vol.  vi.  p.  428:  1882. 

2  For  the  composition  of  xanthin,  see  Emil  Fischer,  Ann.  d.  Chem.  u. 
PAarm.,  vol.  ccxv.  p.  253 :  1882;  Ber.  d.  deutsch,  chem.  Ges.,  vol.  xv.  p.  453: 
1882 ;  and  Arm.  Gautier,  Compt.  rend.,  vol.  xcviii.  p.  1523 :  1884  (Synthesis  of 
xanthin). 

•■'  J.  Piccard,  loc.  cit.;  Kossel,  Zeitschr.  f.  physiol.  Chem.,  vol.  vii.  p.  16 : 
1882;  vol.  viii.  p.  404:  1884. 

^  Kossel,  ibid.,  vol.  x.  p.  250:  1886. 

*  Neubauer,  Zeitschr.  f.  analyt.  Chem.,  vol.  vii.  p.  225  :  1868. 

*  Vide  Stadthagen,  Virchow's  Arch.,  vol.  cix.  p.  390:  1887.  An  account  of 
the  literature  on  the  xanthin  bodies,  and  the  part  they  play  in  the  formation  of 
uric  acid,  is  given  here. 


THE    XANTHIN    BASES  315 

to  say  anything  concerning  their  function,  we  must  expect  that 
the  knowledge  of  their  properties  will  in  the  near  future  open 
up  a  whole  series  of  important  questions.  According  to  the 
most  recent  researches  of  Emil  Fischer,  the  constitution  of  the 
xanthin  bases  may  be  represented  as  follows  : 

HN  — CO  HN  — CO 

CO   C  — IfH  HN  =  C       C  — NH 

I  \  PTT  \  PIT 

1  II  yy^^  I  //^°' 

HN—  C—  N^  HN  —  C—  N^ 

Xanthin.  Guanin. 

HN  — CO  N  =  C  — NH, 

HC       C  — HH  HC       C  — NH 

II        11         >C!H  II       I  \CH 

N  — C— N'^  N— C^N'«^ 

Hypoxanthin.  Adenin. 


LECTURE  XXI 

THE   FUNCTIONS   OF   THE   KIDNEYS,    AND   THE    COMPOSITION 
OF   THE   UEINE 

In  the  last  lecture  we  became  acquainted  with  the  end- 
products  in  which  the  bulk  of  the  nitrogen  leaves  the  body- 
through  the  kidneys.  The  elimination  of  the  nitrogenous  end- 
products  of  metabolism  is  not,  however,  the  sole  function  of  the 
kidneys.  To  the  kidneys  is  assigned  the  duty  of  maintaining 
the  composition  of  the  blood  invariable,  of  rejecting  from  the 
blood  everything  that  does  not  belong  to  it  normally,  whether 
an  abnormal  constituent  or  a  normal  one  that  has  increased 
beyond  its  normal  amount. 

This  function  is  usually  ascribed  to  the  epithelial  cells  of 
the  renal  tubules,  although  it  appears  to  me  that  it  might  with 
equal  justice  be  referred  to  the  cells  of  the  capillary  wall.  There 
is  no  reason  for  assuming  that  the  capillary  wall  plays  a  passive 
part  in  the  process  of  secretion.  We  know  that  it  consists  of 
cells  joined  together  like  mosaic  work,  and  that  each  of  these 
cells  is  a  living  unit,  an  organism  by  itself,  to  which  we  are 
d  priori  justified  in  ascribing  as  complex  functions  as  to  the 
epithelial  cells  of  the  tubules. 

The  cells  of  the  capillary  wall  and  those  of  the  epithelium 
perform  the  work  of  rejecting  the  substances  which  do  not 
normally  form  part  of  the  composition  of  the  blood,  and  this 
they  do  without  regard  to  the  laws  of  diffusion  and  endos- 
mosis  or  to  the  conditions  of  solubility.  They  eliminate 
everything  useless  or  superfluous  —  crystalloid  and  colloid 
substances,  both  soluble  and  insoluble,  both  alkaline  and 
acid. 

Sugar  and  urea  are  both  easily  soluble  in  water  and  readily 
diffusible ;  they  are  both  always  circulating  with  the  blood 
through  the  renal  capillaries.  Sugar,  which  is  an  important 
food-stuff,  is  retained ;  urea,  which  is  an  end-product,  is  excreted. 
The  purpose  is  manifest,  though  we  are  unable  to  explain  the 
reason.  It  does  not  at  present  admit  of  a  mechanical  ex- 
planation. If  the  sugar  exceed  the  normal  quantity,  it  is 
secreted. 

316 


THE    FUNCTIONS    OF    THE    KIDNEYS  317 

Proteins  form  the  main  constituents  of  blood-plasma ;  but 
they  are  never  allowed  to  pass  by  a  healthy  epithelium.  The 
normal  proteids  of  the  plasma  appear  in  the  urine  only  when 
the  renal  epithelium  has  undergone  pathological  alteration,  or 
has  been  impaired  by  impeded  circulation  of  the  blood  and  by 
an  arrest  of  the  supply  of  oxygen.^  But  the  normal  proteids 
of  the  plasma  cannot  pass  the  normal  and  well-nourished 
epithelium ;  and  this  not  by  reason  of  their  colloid  nature,  for 
as  soon  as  a  proteid  that  does  not  belong  to  the  normal  con- 
stituents of  the  plasma,  such  as  egg-albumin  or  a  solution  of 
casein,  is  allowed  to  enter  the  blood,  it  reappears  in  the  urine.^ 
This  applies  not  only  to  colloid  substances,  but  also  to  such  as 
are  absolutely  insoluble  and  immiscible  with  water,  which  are 
removed  by  the  activity  of  the  cells  into  the  commencement  of 
the  renal  tubules,  if  they  do  not  belong  to  the  normal  con- 
stituents of  the  blood.  Among  these  we  may  mention  foreign 
fatty  matters  (cod-liver  oil),  superfluous  Cholesterin,  resins,  and 
the  like. 

If  the  blood  becomes  too  alkaline,  as  it  may  by  conversion 
of  vegetable  salts  of  alkalies  into  carbonates,  the  renal  cells 
separate  the  excess  of  these  carbonates  from  the  blood.  If  the 
alkalescence  of  the  blood  be  diminished  —  perhaps  by  the 
liberation  of  sulphuric  acid  and  phosphoric  acid,  caused  by  the 
decomposition  of  proteids  of  nucleins  and  lecithins — the  renal 
cells  take  up  the  neutral  salts  of  the  blood,  separate  them  into 
acid  and  alkaline,  convey  the  acid  salts  into  the  urine,  and  the 
alkaline  back  into  the  blood,  until  the  normal  alkalinity  is 
restored. 

The  epithelial  cells  are  of  very  varying  form  and  size  in 
different  parts  of  the  urinary  tubules.  This  renders  it  probable 
that  different  portions  have  different  functions  to  perform; 
that  only  certain  constituents  of  the  urine  are  eliminated  by 


1  Heidenhain  in  Hermann's  "  Handbuch  der  Physiol.,"  vol.  v.  pt.  i.  pp.  337, 
371 :  Leipzig,  1883. 

2  J.  Forster,  Zeitschr.  f.  Biolog.,  vol.  xi.  p.  526 :  1875.  In  this  paper  the 
earlier  views  of  Bernard,  Lehmann,  Stokvis,  and  Creile  are  mentioned.  See 
further  R.  Neumeister,  "  Zur  Frage  nach  dem  Schicksal  der  Eiweissnährung  im 
Org2im&m.\xs,"  Sitzungsher.  d.  phys.  med.  Ges.  z.  Würzburg:  1889.  Albuminuria 
occurs  as  a  symptom  of  so  many  and  various  diseases,  and  can  be  caused  in  so 
many  diiferent  ways  that  a  discussion  of  the  subject  is  best  left  to  the  pathologist. 
At  present  chemistry  can  contribute  little  to  the  explanation  of  albuminuria  or  of 
its  relation  to  the  other  symptoms  of  the  diseases  in  which  it  occurs.  A  con- 
nected account  of  our  present  knowledge  of  the  subject  has  been  given  by  H. 
Senator,  "Die  Albuminurie  in  physiologischer  u.  klinischer  Beziehung  u.  ihre 
Behandlung,"  2d  ed.,  Berlin  :  1890.  For  the  methods  of  detection  of  proteid  in 
urine,  I  v/ould  refer  the  reader  to  the  well-known  "Handbuch  d.  physiologisch- 
u.  pathologisch-chemischen  Analyse  "  by  Hoppe-Seyler. 


318  LECTURE    XXI 

one  part,  and  different  ones  by  another.  It  is  known  as  a  fact 
that  the  coloring  matter,  carmine,  when  it  gets  into  the  blood, 
is  excreted  by  the  Malpighian  bodies,^  whereas  indigo  ^  and 
bile  pigments^  are  excreted  by  the  convoluted  tubules  and 
Henle's  loops.  In  birds,  uric  acid  is  found  only  in  the 
epithelium  of  the  convoluted  tubules,  never  in  other  parts.* 
The  purpose  of  this  arrangement  is  evident :  were  the  uric  acid 
to  be  excreted  by  the  Malpighian  bodies,  it  might  remain 
there  and  form  concretions ;  whereas  the  crystals  eliminated  by 
the  convoluted  tubules  are  being  constantly  washed  down  by 
the  fluid  secreted  by  the  glomeruli. 

The  structure  of  the  glomeruli  is  very  puzzling,  and  is  seen 
in  no  other  gland.  The  widening  of  the  arteries  into  the 
capillary  system,  and  their  reunion  to  form  an  efferent  vessel, 
which  is  narrower  than  the  afferent  one,  appear  to  be  arranged 
for  the  purpose  of  slowing  the  blood  and  of  increasing  the 
pressure.  But  we  are  at  present  incapable  of  even  suggesting 
a  theory  as  to  what  significance  this  precaution  has  in  the 
formation  of  urine,  and  as  to  what  constituents  are  formed  or 
eliminated  in  the  glomeruli.  It  has  not  been  found  that  blood- 
pressure  has  any  influence  in  any  part  of  the  body  upon  the 
quantity  and  quality  of  the  transudation  formed.^ 

It  has  hitherto  not  been  proved  that  the  nervous  system 
exercises  any  direct  influence  upon  the  epithelial  cells  of  the 
kidney,  as  it  has  been  ascertained  to  exercise  in  the  case  of  the 
salivary  glands,  and  as  is  also  probable  in  the  case  of  the 
remaining  glands  of  the  digestive  apparatus.  The  renal  nerves 
appear  only  to  act  upon  the  vessels.  This  difference  might 
d  pr^or^  have  been  expected.  The  digestive  glands  form  their 
secretion  from  the  normal  constituents  of  the  blood.  The 
impulse  to  greater  activity  of  the  epithelial  cells  cannot 
therefore  proceed  from  the  blood,  but  from  the  alimentary 
canal,  where  the  need  of  more  secretion  makes  itself  felt ;  this 
necessitates  the  intervention  of  nerves.  The  kidneys  behave 
differently ;  for  the  impulse  to  increased  activity  of  the  renal 
cells  must  proceed  from  the  abnormally  increased  constituents 


■■  Chrzonaczewski,  Virchow's  Arch.,  vol.  xixi.  p.  189:  1864;  Wittich,  Arch. 
/.  mikrosk.  Anat.,  vol.  xi.  p.  77 :  1875. 

'  Heidenhain,  ibid.,  vol.  x.  p.  .30  :  1874 ;  Pfliiger's  Arch.,  vol.  ix.  p.  1 :  1875. 

3  Möbius,  Arch.  f.  Heilk.,  vol.  xviii.  p.  84 :  1877. 

•*"Wittich,  Virchow's  Arch.,  vol.  x.  p.  325:  1856;  Zalesky,  "Unt  über  den 
urämischen  Process  und  die  Function  der  Niere,"  p.  48:  Tübingen,  1865; 
Meissner,  Zeitschr.  f.  rat.  Med.  (3),  vol.  xxxi.  p.  183  :  1867. 

*  Vide  Paschutin,  "  Arbeiten  aus  der  physiologischen  Anstalt  zu  Leipzig," 
p.  197 :  1872 ;  and  Emminghaus,  ibid.,  p.  50 :  1873.  [See  however  remarks  in 
note  on  p.  218.] 


THE    COMPOSITION    OF    UEINE  319 

of  the  blood,   to  remove  which  is  the  duty  of  the  kidneys. 
This  does  not  necessitate  any  nervous  apparatus.^ 

We  should  ä  priori  expect  that  the  kidneys  would  be  all 
the  more  active,  the  more  substances  there  were  in  the  blood 
to  be  excreted,  and  the  greater  the  amount  of  blood  flowing 
through  the  kidneys  in  a  unit  of  time.  All  the  facts  observed 
agree  with  this  view.  Whatever  enlarges  the  lumen  of  the 
renal  vessels  and  increases  the  rapidity  of  the  blood-current, 
such  as  section  of  the  splanchnic  nerve  and  stimulation  of  the 
spinal  cord,  also  increases  the  quantity  of  urine  secreted. 
Whatever  causes  contraction  of  the  vessels  and  diminishes  the 
rapidity  of  the  current,  as  stimulation  of  the  splanchnic, 
mechanical  narrowing  of  the  renal  artery,  or  section  of  the 
cervical  spinal  cord,  also  diminishes  the  urine.  There  is  at 
present  no  ground  for  assuming  that  the  blood-pressure  in  the 
renal  vessels  has  a  direct  influence  upon  the  secretion  of  urine. 

From  these  observations  on  the  functions  of  the  kidneys, 
it  follows  that  the  composition  of  ueine  must  necessarily  be 
a  very  varying  one.  Besides  the  nitrogenous  end-products, 
the  amount  of  which  chiefly  depends  upon  the  proteid  intro- 
duced and  undergoes  great  fluctuations,  the  urine  always  contains 
the  inorganic  salts  which  remain  over  from  the  decomposition 
of  the  organic  food-stuifs,  as  well  as  sulphuric  and  phosphoric 
acids,  which  proceed  from  the  oxidation  and  splitting-up  of 
the  proteids,  nucleins,  and  lecithins ;  and  finally  we  find  in  it 
certain  products  of  metabolism — notably  aromatic  compounds 
and  oxalic  acid — which  are  oxidized  with  difficulty  and  which 
contain  no  nitrogen.  Besides  the  substances  which  occur  in 
large  quantities  and  have  been  subjected  to  careful  investiga- 
tion, there  are  numerous  other  substances  in  the  urine  which 
are  scarcely  known,  as  they  occur  in  such  small  quantities. 
There  is  also  a  large  class  of  substances  which  only  appear 
occasionally  under  certain  normal  and  pathological  conditions 
that  are  little  known ;  and  lastly,  we  meet  with  substances  of 
all  kinds  which  have  been  accidentally  introduced  either  with 
food  or  as  medicines,  and  which  have  not  been  destroyed  in 
the  body. 

In  order  to  give  an  idea  of  the  composition  of  normal  urine, 
two  analyses  are  appended,  which  I  carried  out  on  the  urine 
of  a  young  man  in  good  health,  both  when  on  animal  and  on 
vegetable  diet.^     An  estimate  was  made  of  almost  all  the  con- 

*  Vide  W.  voa  Schröder,  "  Ueber  die  Wirkung  des  Caffeins  als  Diureticum," 
Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxii.  p.  39 :  1886. 

2  The  literature  of  physiology,  so  far  as  I  know,  affords  no  analysis  of  urine 
in  which  all  the  more  important  constituents  were  determined  in  the  same 


320 


LECrUEE   XXI 


stitnents  of  the  urine  which  normally  occur  in  any  quantity. 
After  two  days'  exclusive  diet  of  beef,  the  urine  was  collected 
on  the  second  day.  The  beef  eaten  was  roasted  with  a  little 
salt,  the  only  beverage  being  spring  water.  In  the  second 
case  the  urine  was  also  collected  on  the  second  day,  after  an 
exclusive  diet  of  wheat-bread,  butter,  a  little  salt,  and  spring 
water. 


Composition  of  Twenty -Four  Hours'  Urine  After  a  Diet  of- 


Meat. 
Total  amount  .....  1672        c.cms. 


Urea  .  . 
Uric  acid 
Creatinin 
K2O  .  . 
Na^O.  . 
CaO  .  . 
MgO,  . 
CI  .  . 
SO3'  .    . 


67.2  grms. 
1.398 
2.163 
3.308 
3.991 
0.328 
0.294 
3.817 
4.674 
3.437 


Bread. 
1920         corns. 
20. 6      grms. 
0.253     ■ 
0.961 
1.314 
3.923 
0.339 
0.139 
4.996 
1.265 
1.658 


Both  urines  had  a  strong  acid  reaction.  If  we  calculate  the 
equivalent  of  the  strong  acids  and  bases,  we  find  that  in  both 
the  sulphuric  acid  and  the  chlorin  suffice  by  themselves  to 
neutralize  all  inorganic  bases  : 


3.308  Kfi 
3.991  Na^O 
0.328  CaO 
0.294  MgO 

=  2.177  NajO 
=  3.991  Na^O 
=  0.364  lyXO 
=  0.455  Na^O 

3.817  CI 
4.674  SO3 

4.996  CI 
1.265  SO3 

=  3.337  NajO 
=  3.622  Na^O 

6.959  Na^O 

1.314  KoO 
3.923  Na^O 
0.339  CaO 
0.139  MgO 

6.987  Na^O 
=  0.865  Na^O 
=  3.923  Na^O 
=  0.376  Na^O 
=  0.216  NajO 

=  4.368  NajO 
=  0.980  Na^O 

5.348  NaaO 

6.380  Na,0 

But,  in  addition  to  the  sulphuric  and  hydrochloric  acids, 
the  urines  contain  also  considerable  amounts  of  phosphoric 
and  uric,  besides  some  hippuric  and  oxalic,  acids.  It  would 
therefore  follow  that  they  contain  free  mineral  acids,  had  not 
the  organism  the  means  about  to  be  detailed  of  preventing 


specimen.  I  therefore  venture  to  communicate  these  analyses,  which  were  under- 
taken on  the  occasion  of  certain  experiments  relating  to  metabolism,  and  which 
have  not  yet  been  published. 

^  The  entire  amount  of,  including  the  conjugated,  sulphuric  acid,  was 
determined.  The  urine  was  boiled  with  hydrochloric  acid  and  chlorid  of 
barium. 


URIC    ACID  321 

the  occurrence  of  free  strong  acids  in  the  urine.  In  the  first 
place,  thet-e  is  the  formation  of  ammonia.  In  the  above 
analyses  the  ammonia  has,  unfortunately,  not  been  determined. 
Normal  urine  generally  contains  from  0.4  to  0.9  grm.  In 
order  to  convert  the  1.66  grm.  of  phosphoric  acid  into  the  acid 
ammonia  salt,  exactly  0.4  grm.  of  NHg  suffice ;  0.8  grm.  of 
ammonia  are  equivalent  to  3.44  grms.  of  phosphoric  acid.  A 
second  mode  of  diminishing  the  acidity  of  the  urine  consists  in 
a  portion  of  the  dibasic  sulphuric  acid  being  converted  into  a 
monobasic  acid  by  union  with  aromatic  compounds. 

Normal  urine  becomes  alkaline  only  after  a  vegetable  diet 
containing  potash  salts  of  combustible  acids.  These  are 
largely  present  in  acid  fruits  and  berries  which  contain  the 
acid  potash  salts  of  tartaric,  citric,  malic,  and  other  organic 
acids.  After  combustion  of  the  acids,  the  potash  appears  in 
urine  as  a  carbonate.  The  urine  exhibits  a  strong  alkaline 
reaction,  and  effervesces  on  the  addition  of  acids.  Potatoes 
cause  a  strongly  alkaline  urine,  because  they  contain  little 
proteid  and  therefore  little  sulphuric  acid ;  on  the  other  hand, 
they  contain  much  malate  of  potash,  which  is  converted  into  a 
carbonate.  The  most  important  articles  of  vegetable  diet,  the 
cereals  and  the  leguminosse,  yield  urine  which  is  as  acid  as 
that  due  to  a  diet  of  meat,  because  they  are  rich  in  proteid  and 
phosphates. 

These  observations  afford  some  hints  as  to  the  diet  of 
persons  who  are  predisposed  to  the  formation  of  uric  acid, 
gravel,  and  concretions  in  the  bladder.  I  have  already  shown 
that  we  are  not  fully  acquainted  with  all  the  conditions  of  the 
precipitation  of  uric  acid ;  but  we  do  know  that  the  acidity  of 
the  urine  has  to  be  considered  as  well  as  the  amount  of  uric 
acid.  Patients  should  be  forbidden  food  rich  in  proteid,  and 
poor  in  bases  which  are  able  to  neutralize  the  uric  and  sul- 
phuric acids  formed  from  the  proteid.  Cheese  appears  to  me 
in  this  respect  the  most  injurious  article  of  food.  In  making 
cheese,  the  basic  alkaline  salts  pass  into  the  whey,  and  the 
casein,  on  undergoing  combustion  in  the  organism,  yields 
large  quantities  of  uric,  sulphuric,  and  phosphoric  acids,  which 
are  not  sufficiently  neutralized  by  bases.  In  certain  parts  of 
Saxony,  as  in  Altenburg,  where  the  people  eat  a  great  deal 
of  cheese,  uric  acid  calculi  are  said  to  be  very  common.^ 
Calculus  is  rare  in  Switzerland,  although  cheese  is  also  an 
important  article  of  diet  there,  probably  for  the  reason  that  a 

^  Lehmann,  Sitzung sber.  der  Ges.  f.  Natur  und  Heilkunde  zu  Dresden,  p.  56  : 
1868;  W.  Ebstein  ("  Die  Natur  und  Behandlung  der  Harnsteine,"  pp.  145-156;; 
Wiesbaden,  1884)  gives  a  full  account  of  the  geographical  distribution  of  calculi. 

21 


322  LECTURE   XXI 

considerable  quantity  of  fruit  is  eaten  at  the  same  time.  The 
ingestion  of  salt  meat  and  salt  fish  also  causes  a  very  acid  urine 
containing  much  uric  acid,  because,  in  the  process  of  salting,  the 
basic  salts  (basic  phosphates  and  carbonates  of  the  alkalies)  pass 
into  the  lye,  and  are  replaced  by  neutral  chlorid  of  sodium. 
Russian  physicians  have  informed  me  that  in  certain  districts  of 
their  country,  the  people  living  mainly  on  salt  fish  frequently 
exhibit  uric  acid  calculi.  If  it  be  desired  to  prevent  the  forma- 
tion of  uuic  acid  sediments,  or  to  dissolve  concretions  that  are 
already  formed,  by  the  administration  of  alkalies,  it  is  more 
sensible  to  advise  the  use  of  fruits  and  potatoes  than  to  order 
alkaline  mineral  waters,  the  continued  use  of  which  may  produce 
disturbances  which  we  are  unable  to  estimate.  Because  the 
combination  of  uric  acid  and  lithia  is  more  soluble  in  water 
than  its  combination  with  soda  or  potash,  it  has  been  thought 
necessary  to  treat  the  uric  acid  diathesis  with  a  few  decigrammes 
of  carbonate  of  lithia,  or  even  with  mineral  waters  containing 
one  centigramme  of  lithia  to  the  liter.  This  naive  idea  simply 
implies  ignorance  of  Berthollet's  law.  We  know  that,  in  solu- 
tions of  bases  and  acids,  every  acid  is  distributed  to  all  the 
bases  in  proportion  to  their  quantity.  It  follows  that  only  the 
very  smallest  portion  of  uric  acid  will  combine  with  the  lithia, 
the  largest  proportion  combining  with  the  preponderating  quan- 
tity of  soda,  which  we  introduce  as  chlorid  of  sodium.  The 
largest  proportion  of  lithia  will  reappear  in  the  urine,  united 
with  the  chlorin  of  the  chlorid,  with  sulphuric  and  phosphoric 
acids.  There  will  be  no  increase  in  the  solubility  of  the  uric 
acid. 

It  is  well  known  that  under  pathological  conditions  urine 
may  become  alkaline,  by  the  conversion  of  urea  into  carbonate 
of  ammonia.  This  change  always  takes  place  when  urine  has 
been  exposed  to  the  air  for  some  time,  and  is  effected  by 
certain  forms  of  bacteria.^  If  these  organisms  reach  the 
bladder,  the  conversion  may  begin  there ;  the  urine  becomes 
alkaline,  and  the  alkaline  earths,  which  were  held  in  solution  in 
the  acid  urine,  are  precipitated  as  phosphate  of  lime  and  triple 


1  P.  Cazeneuve  et  Ch.  Livon,  Compt.  rend.,  vol.  Ixxxv.  p.  571 :  1877  ;  R.  von 
Jaksch,  Zeitschr.  f.  physiol.  Chem.,  vol.  v.  p.  395:  1881;  W.  Leube,  Ritzungsber. 
d.  phys.  med.  Soc.  zu  Erlangen,  Nov.  10,  1884,  p.  4 ;  and  Virchow's  Arch.,  vol.  c. 
p.  540 :  1885.  The  ferment  may  be  extracted  from  the  bacteria,  but  during  life 
they  do  not  yield  it  to  the  surrounding  fluid  {Maaculas, Compt.  rend.,  vol.  Ixxviii. 
p.  132:  1874;  and  Pfliiger's  ylrcA.,  vol.  xii.  p.  214 :  1876;  A.  Sheridan  Lea,  i/owrn. 
of  Physiol.,  vol.  vi.  p.  136:  1885).  It  appears  therefore  that  in  the  conversion 
of  urea  into  carbonate  of  ammonia,  chemical  potential  energy  is  converted  into 
kinetic  energy,  and  this  kinetic  energy  is  used  in  the  vital  processes  by  the  fer- 
mentative organisms. 


PIGMENTS  323 

phosphate  of  magnesia.  In  this  way  urinary  calculi  may  be 
formed. 

We  have  now  become  acquainted  with  all  the  ingredients  of 
any  importance  constituting  normal  urine.  Of  the  innumerable 
substances  which,  besides  these,  are  found  in  small  quantities,  I 
will  describe  a  few,  so  far  as  we  have  any  definite  knowledge  of 
their  origin  and  significance. 

First,  the  coloring  matters.  Physicians  have  long  ob- 
served the  remarkable  diiferences  in  the  color  of  urine  under 
various  normal  and  pathological  conditions,  and  have  tried  to 
avail  themselves  of  these  diiferences  for  diagnostic  purposes. 
The  numerous  endeavors  to  isolate  the  coloring  matters  and 
to  study  their  properties  led  to  no  results,  because  the  quan- 
tity was  always  too  small.  We  have  therefore  been  obliged 
to  content  ourselves  with  applying  Greek  and  Latin  names 
to  these  numerous  pigments,  with  which  I.  will  not  trouble  the 
reader,  excepting  with  regard  to  the  only  one  of  which  we 
know  the  composition  and  mode  of  origin.  I  refer  to  urobilin, 
which  was  discovered  by  Jaife.^  He  found  this  reddish  brown 
coloring  matter  constantly  in  normal  urine,  and  in  increased 
quantities  in  febrile  urine.  Its  absorption-spectrum  and  the 
green  fluorescence  which  its  ammoniacal  solution  assumes, 
especially  after  the  addition  of  chlorid  of  zinc,  are  charac- 
teristic. The  composition  of  this  pigment,  which  can  only 
be  obtained  in  very  small  quantities  from  urine,  would  not 
have  been  known  had  not  Maly^  succeeded  in  producing  it 
artificially  by  the  action  of  nascent  hydrogen  upon  bilirubin, 
the  chief  coloring  matter  of  bile.^  This  fully  explains  the 
invariable  presence  of  urobilin  in  the  contents  of  the  intestine, 
as  we  have  seen  that  nascent  hydrogen  constantly  acts  there 
upon  the  bile-pigment.  Human  feces  are  colored  brown  chiefly 
by  urobilin,  and  rarely  contain  any  unaltered  bile-pigment. 
It  is  quite  possible  that  the  urobilin  occurring  in  urine  is 
also  derived  from  the  intestine,  though  we  are  not  forced  to 
this  assumption,  as  urobilin  might  also  be  formed  in  other  or- 
gans. As  a  matter  of  fact,  Jaffe  found  urobilin  in  human  bile. 
Hoppe-Seyler  *  has    since   shown   that  urobilin   may   also    be 

^  M.  Jaflfe,  Virchow's  Arch.,  vol.  xlvii.  p.  405  :  1869  ;  and  Centralbl.  f.  d.  med. 
Wissensch.,  p.  241 :  1868  ;  p.  177  :  1869  :  and  p.  465  :  1871. 

2R.  Maly,  Centralbl.  f.  d.  med.  Wissensch.,  No.  54:  1871 ;  Annal.  d.  Chem., 
vol.  clxiii.  p.  77  :  1872. 

^  [It  has  been  shown  by  Garrod  and  Hopkins  {Journ.  Physiol.,  vol.  Ixxii.  p. 
451 :  1897)  that  in  spite  of  the  close  similarity  in  physical  characters,  the  urobilin 
of  urine  and  feces  has  a  diflerent  constitution  to  that  of  the  hydrobilirubin  of 
Maly.  Whereas  the  latter  contains  about  9  per  cent,  nitrogen,  urobilin  only 
contains  about  4  per  cent.] 

■*  Hoppe-Seyler,  JBer.  d.  deutsch,  chem.  Ges.,  vol.  vii.  p.  1065:  1874. 


324  LECTURE   XXI 

formed  by  the  action  of  nascent  hydrogen  upon  hematm.  We 
thus  arrive  at  a  simple  genetic  connection  between  the  three 
coloring  matters :  ^ 

Hematin CgjHajN^O^Fe 

Bilirubin CsjHjgN^Og 

Urobilin  [or,  rather,  hydrobilirubin] CajH^oN^O^J 

Indigo^  is  generally  regarded  as  belonging  to  the  urinary 
coloring  matters,  although  it  does  not  occur  as  such  in  urine, 
but  as  a  colorless  compound,  as  an  alkaline  indoxyl-sulphate.^ 
If  concentrated  hydrochloric  acid,  with  an  oxidizing  agent  like 
chlorid  of  lime  or  bromin  water,  be  added  to  urine,  the  con- 
jugated sulphuric  acid  is  split  up,  and  the  indoxyl  is  oxidized 
into  indigo : 

2C8H6NKSO,  +  Oj  =  CieHioN^Oj  +  2HKS0i 
Indoxyl-sulphate  of  potash.  Indigo  blue. 

The  amount  of  indigo  thus  formed  is  generally  very  small, 
but  is  seldom  entirely  absent  from  human  urine.  On  shaking 
the  coloring  matter  with  chloroform,  a  beautiful  blue  solution 
is  obtained. 

We  are  not  in  doubt  as  to  the  origin  of  indigo  in  the  animal 
body,  since  we  know  that  indol,  which  is  the  basis  of  the  entire 
indigo-group,  is  obtained  by  bacterial  putrefaction  of  proteid, 
and  is  uniformly  found  in  the  intestinal  contents.*  The  reab- 
sorbed indol  is  oxidized  in  the  tissues  into  indoxyl.  This  process 
is  completely  analogous  to  the  conversion  of  benzol  by  oxidation 
into  phenol. 

CgH^N  +  O  =  CgHgCOH)^ 
Indol.  Indoxyl. 

Indoxyl  combines,  like  most  of  the  aromatic  hydroxylized 
compounds  (phenol,  cresol,  pyrocatechin,  etc.),  with  sulphuric 
acid,  undergoing  dehydration  (p.  256).  Jaffe^  showed  that, 
after  the  subcutaneous  injection  of  indol,  the  conjugated  indoxyl 
compound  reappears  copiously  in  the  urine. 

'  This  genetic  connection  is  more  fully  discussed  in  the  next  lecture,  as  well 
as  the  appearance  of  blood  and  bile-pigments  in  the  urine  under  pathological 
conditions. 

2  On  the  synthesis  and  chemical  constitution  of  indigo,  vide  A.  Baeyer,  Ber. 
d.  deutsch,  ehem.  Ges.,  vol.  xiii.  p.  2254:  1880;  and  vol.  xiv.  p.  1741 :  1881. 

^E.  Baumann  and  L.  Brieger,  Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  254: 
1879.  The  older  literature  on  the  indigo-forming  substance  of  the  urine  is 
appended. 

*S.  Radziejewsky,  Du  Bois'  Arch.,  p.  37:  1870 ;  W.  Kühne,  Ber.  d.  deutsch, 
chem.  Ges.,  vol.  viii.  p.  206:  1875;  Nencki,  ibid.,  vol.  viii.  p.  336:  1875;  Sal- 
kowski,  Zeitschr.  f.  physiol.  Chem.,  vol.  viii.  p.  417 ;  and  vol.  Ixxii.  p.  8 :  1884. 

^  M.  Jafie,  Virchow's  Arch.,  vol.  Ixx.  p.  72 :  1877. 


ETHEREAL    SULPHATES  325 

In  cases  of  intestinal  obstruction  a  larger  quantity  of  the 
indoxyl  compound  has  been  found  in  the  urine.  It  is  quite 
possible  that  this  occurrence  of  large  quantities  of  indigo  might 
be  utilized  for  diagnosis,  by  enabling  us  to  determine  in  which 
section  of  the  intestine  the  obstruction  had  taken  place.  Jaffe 
has  shown,  for  instance,  that  the  increase  in  the  secretion  of 
indoxyl  occurred  in  dogs  after  ligature  of  the  small,  but  not 
after  ligature  of  the  large,  intestine.  This  is  explicable  from 
the  fact  that  proteid,  which  yields  the  material  for  the  formation 
of  indol,  is  absorbed  before  reaching  the  large  intestine.  When 
the  small  intestine  is  ligatured,  the  proteid  stagnates  and  under- 
goes putrefaction.  Corresponding  with  this,  JafFe  has  observed 
an  increased  excretion  of  the  indoxyl  compound  in  man  occur- 
ring only  in  obstruction  of  the  small,  and  not  in  fecal  ob- 
struction of  the  large,  intestine.  This  is  explained  by  the 
fact  that  the  proteids,  which  furnish  the  indol  by  their  putre- 
faction, are  all  absorbed  before  they  reach  the  large  intestine. 
Similarly  Baumann  has  observed  an  increased  excretion  of  the 
indoxyl  compound  in  men  in  cases  of  obstruction  of  the  small 
intestine,  but  never  in  cases  of  fecal  obstruction  of  the  large 
intestine. 

All  the  other  aromatic  compounds  which  occur  in  the  urine 
as  ETHEREAL  SULPHATES  arise,  like  the  indol,  from  putrefaction 
of  proteid  in  the  intestine.  Baumann  ^  has  shown  that  if  a 
dog's  intestine  is  cleared  out  and  disinfected  by  the  administra- 
tion of  calomel,  the  ethereal  sulphates  entirely  disappear  from 
the  urine.  If,  on  the  other  hand,  the  putrefactive  processes 
in  the  intestine  are  increased  by  neutralizing  the  antiseptic 
hydrochloric  acid  of  the  gastric  juice  by  the  administration 
of  calcium  carbonate,  we  get  an  increased  amount  of  the 
ethereal  sulphate  in  the  urine.^  We  thus  see  that  an  estima- 
tion of  these  acids  in  the  urine  may  be  of  great  value  as 
a  means  of  diagnosis,  since  we  gain  an  insight  into  the  intensity 
of  the  putrefactive  changes  in  the  alimentary  canal.  Thus,  for 
example,  if  it  be  wished  to  disinfect  the  intestine  previous  to 
resecting  it,  we  can  determine  when  this  is  effected,  by  noting 
the  time  when  the  ethereal  sulphates  disappear  from  the 
urine.^ 

The  question  now  arises  :  where  and  in  what  organs  does 

1  E.  Baumann,  "  Die  aromatischen  Verbindungen  im  Harne  und  die  Darm- 
fäulniss,"  Zeitschr.  f.  physiol.  Chem.,  vol.  x.  pp.  123-133  :  1886.  We  particularly 
recommend  this  short  and  lucid  statement  of  Baumann's  to  the  student. 

2  A.  Kast,  "  Ueb.  d.  quantitative  Bemessung  der  antiseptischen  Leistung  des 
Magensaftes,"  "  Festschr.  z.  Eröffnung  d.  neuen  allg.  Krankenhauses  zu  Ham- 
burg-Eppendorf "  :  1889. 

^  A.  Kast  und  H.  Baas,  3Iünchener  med.  Wochenschrift,  No.  4:  1888. 


326  LECTURE   XXT 

the  conjugation  of  the  aromatic  compounds,  formed  in  the  in- 
testine, with  sulphuric  acid  take  place?  This  much  is  certain, 
that  it  does  not  primarily  take  place  in  the  kidney,  for  after 
the  administration  of  phenol,  phenolsulphuric  acid  is  found  in 
the  blood/ 

Phenol  is  a  violent  poison,  but  the  phenolsulphate  does  not 
exert  toxic  effects.  Baumann  therefore  recommends  sulphate  of 
soda  as  an  antidote  to  phenol-poisoning.  He  found  that  when 
phenol  was  applied  to  a  dog's  skin,  the  animal  bore  the  poison 
better  and  yielded  more  phenolsulphuric  acid,  when  at  the  same 
time  sulphate  of  soda  was  administered.  This  would  not  be  in- 
telligible if  the  combination  primarily  occurred  in  the  kidney. 

Baumann  found  a  much  larger  amount  of  ethereal  sulphates 
in  the  liver  than  in  the  blood.  This  renders  it  probable  that 
the  synthesis  occurs  in  the  liver ;  that  the  poisonous  aromatic 
compounds  reaching  it  from  the  intestine  are  here  subject  to  a 
transformation  into  innocuous  combinations  before  entering  the 
general  circulation  (vide  Lecture  XVIII.). 

As  yet  we  have  only  become  acquainted  with  two  sorts  of 
compounds  of  sulphur  as  constituents  of  the  urine :  the  salts  of 
the  ordinary  dibasic  and  of  the  monobasic  conjugated  sulphuric 
acids.  The  quantity  of  sulphuric  acid  occurring  in  the  latter 
form  in  human  urine  averages  one-tenth  of  the  amount  of 
ordinary  sulphuric  acid.^  But  there  is  a  much  larger  number 
of  sulphur  compounds  in  the  urine.  If  urine  acidulated  with 
acetic  acid  is  precipitated  with  chlorid  of  barium,  the  ordinary 
sulphates  are  precipitated.  If  we  now  boil  the  filtrate,  rendered 
strongly  acid  by  the  addition  of  hydrochloric  acid,  the  ethereal 
sulphates  are  broken  up,  and  this  portion  of  sulphuric  acid  may 
also  be  precipitated  as  a  salt  of  barium.  If  this  filtrate  is  now 
evaporated  to  dryness  and  fused  with  saltpeter,  we  again  obtain 
a  considerable  amount  of  sulphuric  acid.  This  third  group  of 
sulphur  compounds  contains  from  10  to  20  per  cent,  of  all  the 
sulphur  excreted  in  human  urine.  In  dogs  and  rabbits,  the 
quantity  of  these  organic  compounds  of  sulphur  is  much  larger.' 
Let  us  now  consider  what  is  really  known  about  these  organic 
sulphur  compounds,  and  their  relation  on  the  one  hand  to  pro- 
teid,  and  on  the  other  to  sulphuric  acid. 

^  Baumann,  Pflüger's  Arch.,  vol.  xiii.  p.  285:  1876. 

2E.  V.  d.  Velden,  Virchow's  Arch.,  vol.  Ixx.  p.  343:  1877. 

^  See  Voit  and  Bischofif,  "  Die  Gesetze  der  Ernährung  des  Fleischfressers,"  p. 
279:  Leipzig,  1860;  Voit,  Zeitschr.  f.  Biolog.,  vol.  i.  p.  127:  1865;  vol.  x.  note 
to  p.  216:  1874;  Salkowski,  Virchow's  Arch.,  vol.  Iviii.  p.  460:  1873;  Kunkel, 
Pflüger's  Arch.,  vol.  xiv.  p.  344 :  1877  ;  R.  Lepine,  Guerin  et  Flavard,  Revue  de 
Medecine,  vol.  i.  pp.  27,  911 :  1882;  St.  Bondzynski  and  R.  Gottlieb,  Centralbl.  f. 
d.  med.  Wissenach.,  No.  33:  1897. 


CYSTIN  327 

It  is  net  much  we  know,  but  we  will  endeavor  to  collect 
and  review  the  fragments  of  our  knowledge. 

We  are  compelled  to  assume  at  least  two  atoms  of  sulphur 
in  a  molecule  of  proteid,  one  oxidized  and  the  other  unoxidized.^ 
If  we  heat  proteid  with  potash,  one  sulphur  atom  goes  to 
form  sulphid  of  potash,  the  other  forms  sulphate  of  potash. 
The  former  may  be  easily  recognized  on  boiling  with  an 
alkaline  solution  of  lead  oxid  when  it  is  precipitated  as  lead 
sulphid.  The  proteids  such  as  casein,  the  proteid  moiety  of 
hemoglobin  or  legumin,  which  are  poorer  in  sulphur,  do  not 
give  this  reaction.  Among  the  organic  decomposition-prod- 
ucts of  proteid  in  the  animal  body,  we  meet  with  the  oxidized 
atom  of  sulphur  in  taurin,  with  the  unoxidized  in  cystin. 
If  we  boil  cystin  with  an  alkaline  solution  of  oxid  of  lead,  a 
black  sulphid  of  lead  is  thrown  down.  Of  course  taurin, 
which  we  have  already  shown  to  be  amido-ethylsulphonic  acid 
(p.  178),  cannot  give  this  reaction. 

Cystin  has  the  formula  C3HgNS02.^  It  does  not  occur  in 
the  normal  organism.^  We  are  not  yet  acquainted  with  the 
abnormal  conditions  under  which  a  large  amount  of  the  sulphur 
is  secreted  in  the  urine  as  cystin.  It  appears  however  that 
even  in  normal  metabolism,  in  the  course  of  the  formation  of 
sulphuric  acid  products,  a  body  is  formed  which  is  closely  allied 
to  cystin,  and  is  distinguished  from  it  only  by  an  additional 
atom  of  hydrogen,  viz.,  cystein.  A  substituted  cystein,  for 
instance,  appears  in  the  urine  of  dogs  after  the  administration 
of  brombenzol.  Baumann,*  to  whom  we  are  indebted  for  the 
most  searching  inquiries  into  the  origin  of  cystin,  regards  cys- 
tein as  a  lactic  acid,  in  which  H  is  replaced  by  NH«,  and  the 
OH  by  SH— 

CH3 

i\ 
I   ^SH 

COOH 


^  The  latest  and  most  careful  researches  on  the  condition  of  the  sulphur  in 
proteids  have  been  carried  out  by  A.  Krüger  (Pflüger's  Arch.,  vol.  xliii.  p.  244: 
1888).  Unfortunately,  Krüger  did  not  make  use  of  pure  material  for  his 
researches. 

2  E.  Külz,  Zeitschr.  f.  Biolog.,  vol.  xx.  p.  1  :  1884. 

2  Stadthagen,  Zeitschr.  f.  physiol.  Chem.,  vol.  ix.  p.  129  :  1884. 

*  E.  Baumann  and  C.  Preusse,  Ber.  d.  dexUsch.  chem.  Ges.,  vol.  xii.  p.  806: 
1879 ;  Zeitschr.  f.  physiol.  Chem.,  vol.  v.  p.  309  :  1881 ;  M.  Jaffe,  Ber.  d.  deutsch, 
chem.  Ges.,  vol.  xii.  p.  1092 ;  1879  ;  Baumann,  ibid.,  vol.  xv.  p.  1731 :  1882  ; 
Zeitschr.  f.  physiol.  Chem.,  vol.  viii.  p.  299  :  1884.  Vide  also  E.  Goldmann,  ibid., 
vol.  ix.  p.  260  :  1884. 


328  LECTURE    XXI 

The  substituted  cystein  which  appears  in  the  urine  after  ad- 
ministration of  brombenzol  when  boiled  with  dilute  acids,  is 
broken  up,  with  hydration,  into  acetic  acid  and  bromphenyl- 
cystein — 

CH3 


h 


^S(CeH,Br) 
COOH 


Baumann  obtained  cystein  from  cystin  by  the  action  of  nascent 
hydrogen.  The  oxygen  of  atmospheric  air  reconverts  the 
cystein  into  cystin. 


? 


H2N  — C  — SH  +  O  +  HS 


OOH 


The  empirical  formula  of  cystiu  must  therefore  be  doubled : 
0^11^21^2820^.  The  origin  of  cystin  in  the  animal  body  is  prob- 
ably due  to  a  synthetic  process,  and  possibly  two  molecules  of 
proteid  always  yield  the  material  for  the  formation  of  one 
molecule  of  cystin. 

The  formation  of  bromphenylcystein  would  accordingly  be 
a  process  quite  analogous  to  that  of  cystin.  Here  again  a 
divalent  oxygen  atom  takes  a  hydrogen  atom  from  cystin  and 
from  brombenzol,  and  effects  the  linking  of  the  liberated 
affinities — 


CH3  CH3 

H,N  —  C  —  SPI  +  O  +  HCe H,Br  =  HjO  +  H^N -  C  —  S(C6H,Br) 
COOH  COOH 


Cystin  does  not  dissolve  readily  in  water,  it  therefore 
always  occurs  in  urine  as  a  sediment,  and  very  occasionally 
causes  the  formation  of  vesical  calculi.  There  are  some  people 
who    secrete   a  large    quantity    (about    one-quarter)     of    the 


TÄUBIN  329 

sulphur  as- cystin,  without  exhibiting  any  derangement  in  their 
health.  This  rare  anomaly  of  metabolism  sometimes  occurs, 
probably  as  the  result  of  heredity,  in  several  members  of  the 
same  family/ 

Under  normal  conditions  cystin,  or  its  antecedent  cystem, 
breaks  up  still  further  and  is  oxidized,  and  the  greater  portion 
of  its  sulphur  appears  in  the  urine  as  sulphuric  acid.  This  is 
confirmed  by  an  experiment  made  in  Baumann's  laboratory  by 
Goldmann.^  He  gave  a  little  dog  2  grms.  of  cystein,  and 
found  that  the  greater  portion,  about  two-thirds,  appeared  as 
sulphuric  acid  in  the  urine.  The  remainder  had  served  to  in- 
crease the  organic  sulphur  compounds  in  the  urine.  This  view, 
that  the  larger  portion  of  the  sulphur  of  cystein  is  converted  by 
oxidation  into  sulphuric  acid,  is  confirmed  by  the  fact  that  in  the 
cystinuria  of  man,  the  urine  has  generally  an  alkaline  or  very 
feebly  acid  reaction. 

"VVe  know  little  positively  with  regard  to  the  fate  of  tauein 
[CH2(NH2)  -  CH2SO3H] .  ■  I  have  already  stated  that  the 
amount  of  sulphur  which  occurs  as  taurin  in  bile  constitutes 
only  a  minute  portion  of  the  sulphur  of  the  decomposed  pro- 
teid,  and  is  only  slightly  increased  if  more  proteid  is  taken 
(compare  p.  182).  It  is  questionable  therefore  whether  a  taurin 
molecule  results  from  each  molecule  of  proteid.  In  bile,  taurin 
is  conjugated  with  cholalic  acid.  In  the  intestine,  the  ferments 
of  digestion  and  putrefaction  doubtless  cause  this  compound 
to  break  up  with  hydration.  We  do  not  know  whether  the 
liberated  taurin  is  absorbed  as  such,  or  after  previous  change. 
We  have  not  been  able  as  yet  to  prove  its  presence  in  the 
feces  or  in  the  urine.  No  satisfactory  results  have  been  ob- 
tained with  regard  to  the  further  destination  of  taurin  from 
experiments^  consisting  in  its  artificial  introduction  into  the 
body.  If  large  quantities  of  taurin  are  administered  to  man  or 
dogs,  the  process  of  absorption  does  not  take  place  slowly 
enough  to  allow  of  its  complete  change  into  the  normal  end- 
products  ;  one  portion  of  the  taurin  appears  as  such  in  the  urine, 
another  as  a  substituted  urea — 


'  F.  W.  Beneke,  "Grundlinien  der  Patliologie  des  Stofiweelisels, "  p.  255 
Berlin,  1874.  Compare  also  A.  Niemann,  Detitsch.  Arch.  f.  Min.  3Ied.,  vol 
xviii.  p.  232:  1876;  W.  F.  Löbisch,  Liebig's  Annal.,  vol.  clxxxii.  p.  231 :  1876 
W.  Ebstein,  "  Die  Natur  und  Behandlung  der  Gicht,"  p.  130 :  Wiesbaden,  1882 
and  "Die  Natur  und  Behandlung  der  Harnsteine,"  p.  172:  Wiesbaden,  1884 
Stadthagen,  Virchow's  Arch.,  vol.  c.  p.  416  :  1885. 

2  E.  Goldmann,  Zeitschr.  f.  physiol.  Ckem.,  vol.  ix.  p.  269  :  1885. 

3  E.  Salkowski,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  vi.  pp.  744, 1191, 1312  :  1873  ; 
and  Virchow's  Arch.,  vol.  Iviii.  p.  460  :  1873. 


330  LECTURE   XXI 


=0 


H 

CHn  —  CHo  —  SOqH 


The  presence  of  this  substituted  urea  has  not  so  far  been 
positively  demonstrated  in  normal  urine.  In  the  rabbit,  it  is 
not  found  even  after  the  artificial  introduction  of  taurin.  Al- 
most all  the  sulphur  of  the  taurin  reappears  as  sulphuric  and 
THiosuLPHUEic  acid  in  the  urine  of  these  animals.  The  con- 
version into  thiosulphuric  acid  however  occurs  only  when  the 
taurin  is  introduced  into  the  stomach ;  if  it  is  injected  sub- 
cutaneously,  the  greater  part  reappears  unaltered  in  the  urine. 
The  thiosulphuric  acid  is  evidently  formed  by  the  processes  of 
reduction  taking  place  in  the  intestine.  In  the  normal  urine 
of  rabbits,  thiosulphuric  acid  has  not  been  found,  though  it 
occurs  frequently  in  that  of  cats  and  dogs.^  In  human  urine, 
it  has  only  been  once  found  in  typhoid.^ 

SuLPHOCYANic  AciD,^  (CNSH),  also  belongs  to  the  sulphur 
compounds  occurring  in  the  urine.  Gscheidlen  found  these 
acids  constantly  in  human  urine,  and  in  that  of  horses,  cattle, 
dogs,  cats,  and  rabbits.  On  an  average,  one  liter  of  human 
urine  contained  0.02  grm.  Munk  found  the  average  of  three 
determinations  to  be  0.08  grm.  Sulphocyanates  were  also  found 
in  dogs'  blood.  Gscheidlen  proved  that  they  are  derived  from 
the  salivary  glands.  The  saliva  of  mammals  invariably  con- 
tains small  quantities  of  sulphocyanates.  Gscheidlen  and 
Heidenhain  divided  all  the  ducts  of  the  salivary  glands  in 
dogs,  and  thus  prevented  the  saliva  from  entering  the  mouth. 
The  alkaline  sulphocyanate  was  now  found  to  have  disappeared 
from  the  blood  and  the  urine ;  although  it  was  still  present  in 
the  saliva  flowing  from  the  wounds.  It  follows  that  in  the 
normal  condition  sulphocyanic  acid  is  formed  in  the  salivary 
glands,  passes  with  the  saliva  into  the  intestinal  canal,  whence 
it  is  absorbed  into  the  blood  and  appears  in  the  urine.     We 


■^  O.  Schmiedeberg,  Arch.  d.  Heilk.,  vol.  viii.  p.  422:  1867;  Meissner, 
Zeitschr.f.  rat.  Med.,  vol.  xxxi.  p.  322:  1868. 

2  Ad.  Strümpell,  Arch.  d.  Heilk.,  vol.  xvii.  p.  390:  1876. 

^Leared,  Proc.  Roy.  Soc,  vol.  xvi.  p.  18:  1870;  Gscheidlen,  Tageblatt  d. 
47  Vers.  d.  Naturf.  u.  Aerzte  in  Breslau,  p.  98  :  1874 ;  and  Pfliiger's  Arch.,  vol. 
xiv.  p.  401 :  1877 :  Kiilz,  Sitztingsber.  d.  Ges.  z.  Bef'order.  d.  ges.  Naturw.  in 
Marburg,  p.  76:  1875;  J.  Munk,  Virchow's  Arch.,  vol.  Ixix.  p.  354:  1877. 


OXALIC   ACID  331 

are  ignorant  as  to  the  significance  of  these  small  quantities  of 
sulphocyanic  acid  in  the  functions  of  the  saliva,  or  in  any  other 
processes  of  the  organism. 

Of  the  organic  constituents  of  the  urine,  only  those  which 
are  free  from  sulphur  and  nitrogen  remain  for  our  consideration. 
Lactic  acid,  sugar  and  oxalic  acid  belong  to  this  class. 
Lactic  acid  however  has  never  been  detected  with  certainty  in 
normal  urine.  It  has  only  been  found  in  phosphorus-poison- 
ing, atrophy  of  the  liver,^  osteomalacia,^  and  trichinosis.^  On 
teleological  grounds,  we  must  doubt  whether  lactic  acid  passes 
into  normal  urine,  as  this  would  be  a  waste  of  potential  energy. 
The  same  argument  applies  in  a  still  more  forcible  manner  to 
sugar.  All  analyses  of  normal  urine  have  the  more  positively 
shown  the  absence  of  sugar,  the  more  carefully  the  investiga- 
tion was  carried  out.  Even  those  writers  who  assert  the  pres- 
ence of  sugar  in  normal  urine,  admit  that  they  have  only  suc- 
ceeded in  finding  it  in  very  minute  quantities.* 

Oxalic  acid  is  a  constant  ingredient  in  normal  human 
urine  after  a  mixed  diet,  but  it  never  occurs  except  in  very 
small  quantity,  at  most  0.02  grm.  in  twenty-four  hours'  urine.* 
This  oxalic  acid,  in  all  probability,  arises  from  the  oxalic  acid 
which  is  contained  in  the  vegetable  articles  of  food.  There  is 
at  present  no  sufficient  reason  for  assuming  any  other  source 
for  the  oxalic  acid  of  normal  urine.  I  was  unable  to  detect 
any  oxalic  acid  in  the  urine  of  a  young  man  in  good  health 
after  two  days'  exclusive  diet  of  meat,  nor  in  the  urine  of 
another  healthy  young  man  after  he  had  eaten  nothing  but  fat 
meat  and  sugar.^  It  therefore  appears  that  oxalic  acid  does 
not  normally    arise   from    any  of  the  three  main  classes   of 

'  Schultzen  and  Riess,  Annalen  des  Charite-Krankenhauses,  vol.  xv.:  1869. 

2  Moers  and  Muck,  Deutsch.  Arch.  f.  klin.  Med.,  vol.  v.  p.  485  :  1869.  The 
method  of  testing  used  in  this  experiment  was,  however,  unsatisfactory.  Com- 
pare the  critique  of  Nencki  and  Sieber,  Journ.  f.  prakt.  Chem.,  vol.  xxvi.  p.  41 : 
1882 ;  and  E.  Heuss,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxvi.  p.  147:  1889. 

*  Th.  Simon  und  F.  Wibel,  Ber.  d.  deutsch,  ehem.  Ges.,  vol.  iv.  p.  139  : 
1871. 

•*  In  this  connection  see  E.  Kiilz,  Pfliiger's  Arch.,  vol.  xiii.  p.  269  :  1876 ;  M. 
Aheles,  Centralbl.  f.  d.  med.  Wissensch.,  Nos.  3,  12,22:  1879;  J.  Seegen,  ibid., 
Nos.  8, 16  ;  Regulus  Moscatelli,  Moleschott's  Unters,  zur  Naturlehre  des  Menschen 
u.  d.  Th.,  vol.  xiii.  p.  103:  1881;  L.  v.  Udranszky,  Zeitschr.  f.physiol.  Chem., 
vol.  xii.  p.  377 :  1888  ;  and  Bericht,  d.  naturforsch.  GeseUsch.  z.  Freiburg  i.  B., 
vol.  iv.  part  v.:  1889.  Compare  the  works  quoted  on  pp.  259, 260,  on  glycuronic 
acid. 

*  P.  Fiirbringer,  Deutsch.  Arch.  f.  klin.  Med.,  vol.  xviii.  p.  143 :  1876 ;  an 
account  of  the  literature  on  the  excretion  of  oxalic  acid  is  given  here.  Fiir- 
bringer adopted  Neubauer's  method.  O.  Schultzen  (Du  Bois'  Arch.,  p.  719  : 
1868)  found  higher  values  by  employing  another  method.  A  critique  of  both 
methods  is  given  by  Wesley  Mills,  whose  researches  on  the  subject  were  carried 
out  under  Salkowski,  Virchow's  Arch.,  vol.  xcix.  p.  305  :  1885. 

"  I  made  use  of  Neubauer's  method  in  testing  for  it. 


332  LECTUEE    XXI 

food.  But  the  oxalic  acid  contained  in  vegetable  articles 
of  diet  must  pass  into  the  urine.  Experiments  carried  out 
by  Gaglio^  in  Schmiedeberg's  laboratory  at  Strassburg  show 
that  oxalic  acid  is  not  destroyed  in  the  animal  body.  No 
oxalic  acid  was  excreted  either  by  a  dog  that  was  starving  or 
by  one  that  was  fed  on  meat.^  But  if  only  from  |  to  1  mgrm. 
of  oxalic  acid  or  of  oxalate  of  soda  was  injected  subcutaneously, 
the  presence  of  oxalic  acid  was  demonstrated  in  the  urine 
within  the  next  twenty-four  or  forty-eight  hours.  If  a  neutral 
solution  of  oxalate  of  soda  was  injected  into  the  crop  of  a  cock, 
nearly  all  the  oxalic  acid  was  found  in  the  discharge  of  the 
cloaca. 

Somewhat  different  conclusions  were  arrived  at  by  P. 
Marfori/  who  took  1  to  1.5  grms.  oxalic  acid  and  determined 
the  amount  of  this  substance  excreted  in  the  feces  and  urine. 
Only  a  small  portion  of  the  oxalic  acid  reappeared  in  the 
feces.  So  that  the  greater  part  was  absorbed.  Of  the  amount 
absorbed,  only  4  to  14  per  cent,  could  be  recovered  from  the 
urine. 

It  seems  however  that,  under  abnormal  conditions,''  oxalic 
acid  may  appear  as  the  result  of  metabolism,  owing  to  an 
imperfect  oxidation  of  articles  of  diet.  Medical  literature  con- 
tains numerous  cases  illustrating  increased  excretion  of  oxalic 
acid  in  jaundice,  diabetes,  scrofula,  hypochondriasis,  and  other 
disorders.  We  even  find  oxaluria  spoken  of  as  an  independent 
disease.  But  we  seek  in  vain  for  trustworthy  quantitative 
determinations,  with  due  consideration  of  the  constituents  of 
the  food.  The  conditions  underlying  the  occurrence  of  oxalic 
acid  in  the  urine  have  great  practical  interest,  because  oxalic 
acid  may  lead  to  the  formation  of  calculi.  The  lime  salt  of 
this  acid  is  well  known  to  be  insoluble  in  water ;  hence  this 
salt  is  frequently  to  be  found  in  urinary  sediments  in  the  well- 
known  octahedral  form.     If  the  oxalate  is  precipitated  in  the 


iGaetano  Gaglio,  Arch.f.  exper.  Path.  u.  Pharm.,  vol.  xxii.  p.  246 :  1887. 

2  In  contradiction  to  this  account  of  Gaglio's,  we  find  it  stated  by  W.  Mill 
(Virchow's  Arch.,  vol.  xcix.  p.  305  :  1885)  that  he  detected  minute  quantities  of 
oxalic  acid  in  the  urine  of  dogs  fed  exclusively  on  meat  or  on  meat  and  bacon. 

^PioMarfori,  "Sulle  trasformazioni  di  alcuni  acidi  della  serie  ossalica  nel 
organismo  dell'uomo,"  Milano,  1890. 

*  In  this  respect  we  should  note  the  statements  of  Gaglio,  who  uniformly 
found  oxalic  acid  in  the  urine  of  frogs,  when  he  arrested  their  muscular  move- 
ments by  destruction  of  the  spinal  cord,  by  paralyzing  poisons,  or  by  mere  fix- 
ation {Giornale  della  R.  Accad.  di  Med.  di  Torino,  ji.  178  :  1883);  and  also 
those  of  Hammerbacher,  who  found  the  excretion  of  oxalic  acid  increased  in  dogs 
after  the  administration  of  bicarbonate  of  soda  (Pfliiger's  Arch.,  vol.  xxxiii.  p. 
89,:  1883).  This  effect  of  bicarbonate  of  soda  was  not  confirmed  by  Fiirbringer 
{loc.  cit.)  in  man. 


OXALIC    ACID  333 

bladder,  it  may  lead  to  the  formation  of  vesical  calculi.  The 
solution  of  oxalate  of  lime  in  the  urine  depends  mainly  on  its 
acidity.  A  solution  of  acid  phosphate  of  soda  dissolves  oxalate 
of  lime.^  We  can  thus  explain  how  it  is  that  oxalate  calculi 
sometimes  form  under  similar  conditions  as  phosphatic  calculi, 
and  that  occasionally  vesical  calculi  consist  of  both  ingredients, 
mixed  up  together  or  in  concentric  layers.  I  wish  again  to  lay 
stress  on  the  fact  that  increase  in  the  sediment  of  oxalate  of 
lime  does  not  justify  the  inference  that  there  is  an  increased 
secretion  of  oxalic  acid.  This  erroneous  conclusion  has  led  to 
many  mistakes. 

^  C.  Neubauer,  Arch,  des  Vereins  für  gemeinschaftliche  Arbeiten  zur  Förde- 
rung der  wissenschaftlichen  Heilkunde,  vol.  iv.  pp.  16,  17 :  1858 ;  and  Modder- 
mann,  Nederl.  Tijdschr.:  1864,  summarized  in  Schmidt's  Jahrbücher  der  gesamm- 
ten  Med.,  vol.  cxxv.  p.  145  :  1865. 


LECTURE   XXII 

METABOLISM    IN    THE    LIVER FORMATION    OF 

GLYCOGEN 

We  now  approach  one  of  the  most  involved  and  difficult 
subjects  in  the  whole  range  of  physiological  chemistry :  the 
metabolism  in  the  liver. 

Like  the  kidney,  the  liver  has  to  fulfil  the  function  of 
maintaining  the  uniform  composition  of  the  blood.  While 
the  kidney  removes  all  superfluous  and  foreign  ingredients, 
the  liver  revises  everything  before  it  enters  the  blood.  For 
this  reason,  it  is  interposed  in  the  current  that  passes  from  the 
intestine  to  the  heart.  We  have  seen  how  it  guards  against 
the  blood  being  overwhelmed  with  sugar,  while,  on  the  other 
hand,  it  prevents  a  deficiency  of  this  important  article  of 
nutrition  in  the  blood  (p.  189).  We  have  also  seen  that  it 
is  constantly  converting  ammonia,  which  is  a  virulent  poison, 
into  harmless  compounds,  such  as  urea  and  uric  acid  (pp.  294, 
310).  Similarly,  the  liver  converts  the  equally  poisonous 
aromatic  products  of  putrefaction,  which  originate  from  the 
proteids  in  the  intestine,  into  harmless  compounds,  by  conjuga- 
tion with  alkaline  sulphates  (pp.  256,  326).  We  also  know 
that  many  poisons,  such  as  metals,  alkaloids,^  etc.,  are  arrested 
in  the  liver. 

It  also  appears  that  the  system  of  innervation  of  the  liver 
is  identical  with  that  of  the  kidney.  We  have  not  hitherto 
been  able  to  prove  a  direct  influence  of  nerves  upon  the  hepatic 
cell.  The  functions  of  the  liver,  like  those  of  the  kidney,  are 
regulated  directly  by  the  composition  of  the  blood.  This  fact 
also  indicates  that  the  chief  duty  of  the  liver  consists  in  regu- 
lating the  composition  of  the  blood  (compare  p.  189). 

In  addition  to  this  function,  the  liver,  as  we  have  seen 
above,  performs  that  of  secreting  bile.  We  have  already 
mentioned  the  grounds  for  our  belief  that  bile  is  not  merely 
an  accidental  product  which  is  excreted  during  the  essential 

^  G.  H.  Roger,  Arch.  d.  physiol.  norm,  et  path.,  V.  vol.  iv.  p.  24 :  1892  ;  E. 
Kotliar,  Arch.  d.  Sc.  Mol.,  vol.  ii.  p.  586:  1893. 

334 


METABOLISM    OF    THE    LIVER  335 

changes  taking  place  in  the  liver,  and  removed  by  the  in- 
testine, but  that  is  a  secretion  which  performs  important 
duties  in  the  processes  occurring  in  the  bowel  (vide  supi-a,  pp. 
182-186). 

All  these  facts  tend  to  show  that  the  liver,  the  largest  of 
all  glands,  is  the  seat  of  numerous  and  complex  chemical 
changes.  It  has  been  hoped,  by  comparing  the  composition  of 
the  inflowing  and  outflowing  blood,  to  obtain  an  insight  into 
these  processes,  or  at  least  to  suggest  certain  fruitful  inquiries. 
Numerous  comparative  analyses  have  been  made  of  the  blood  in 
the  portal  and  hepatic  veins.^  But  when  we  consider  how 
large  a  quantity  of  blood  passes  through  the  liver,  and  how 
trifling  the  amount  of  bile  and  lymph  formed  is  in  comparison, 
we  can  scarcely  expect  to  be  able  to  demonstrate  marked  dif- 
ferences in  the  composition  of  the  inflowing  and  outflowing 
blood.  It  is  probable  that  the  differences  in  the  analyses  of 
the  blood  of  the  portal  and  hepatic  veins  are  due  to  experi- 
mental errors,  for  they  have  been  smaller  in  proportion  to  the 
care  bestowed  on  the  analyses,  and,  in  the  most  reliable  deter- 
minations, are  Avithin  the  limits  of  unavoidable  errors. 

Another  method  of  obtaining  an  insight  into  the  processes 
occurring  in  the  liver  would  consist  in  extirpating  that  organ, 
or  at  least  in  isolating  it  from  the  circulation  of  the  blood,  and 
noticing  what  changes  take  place  in  the  animal  metabolism 
as  a  result  of  the  operation.  In  this  way  we  might  hope,  in 
the  first  instance,  to  decide  whether  the  constituents  of  bile,  the 
bile  acids  and  pigments,  are  formed  in  the  liver  or  are  conveyed 
to  it  by  the  blood.  If  the  latter  were  the  case,  the  liver  would 
be  only  an  excretory  organ,  and  its  extirpation  would  cause  an 
accumulation  of  the  biliary  constituents  in  the  blood  and  in  the 
organs. 

We  have  already  seen,  when  discussing  the  question  as  to 
the  locality  of  the  formation  of  hippuric  acid,  that  frogs  survive 
the  extirpation  of  the  liver  for  several  days,  but  the  experi- 
ments which  have  been  carried  out  with  reference  to  the 
present  question,  have  been  inconclusive,  because  the  inquirers 
were  unable  to  overcome  the  difficulties  which  present  them- 
selves in  the  endeavor  to  demonstrate  the  constituents  of  bile 
in  the  organs  of  the  frog.^ 

^  C.  Flügge  gives  a  critical  account  of  these  works,  Zeitschr.f.  Biolog.,  vol. 
xiii.  p.  133 :  1877;  compare  also  W.  Drosdoff,  Zeitschr.  f.physiol.  Chem.,  vol.  i. 
p.  233 :  1877. 

-  These  experiments  are  criticised  by  Hans  Stern,  Arch.  f.  exper.  Path.  u. 
Pharm.,  vol.  xix.  pp.  42-44:  1885.  None  of  the  investigators  has  proved,  by 
control  experiments,  that  he  can  demonstrate  small  quantities  of  biliary  constitu- 
ents in  frog's  tissue. 


336  LECTURE    XXII 

I  have  already  repeatedly  mentioned  that,  on  account  of 
the  accumulation  of  blood  in  the  portal  system  after  extirpa- 
tion or  isolation  of  the  liver  in  mammals,  this  operation  has 
not  as  yet  been  successful  in  them  (p.  295).  In  discussing 
the  formation  of  uric  acid,  we  have  seen  that  this  difficulty 
does  not  present  itself  in  birds,  owing  to  their  possessing 
a  normal  communication  between  the  portal  and  renal 
veins  (p.  310).  Naunyn,  Stern,  and  Minkowski  have  utilized 
this  circumstance,  in  order  to  determine  the  question  as 
to  the  seat  of  the  formation  of  the  biliary  constituents  in 
birds. 

Stern  ^  ligatured  the  bile-ducts  and  all  the  vessels  passing 
to  the  liver  in  pigeons,  including  not  only  the  portal  vein 
and  the  hepatic  artery,  but  also  the  small  veins.  After 
from  ten  to  twenty-four  hours,  the  animals  were  bled  to 
death.  No  secretion  of  urine  had  taken  place  after  the 
operation,  as  renal  activity  always  ceases  in  pigeons  after 
ligaturing  the  liver.^  If  the  biliary  constituents  were  formed 
outside  the  liver,  they  would  now  accumulate  in  the  blood 
and  in  the  tissues,  as  they  would  have  no  exit.  Stern  paid 
special  attention  to  the  bile  pigment,  which  is  easy  of 
detection ;  but  it  was  nowhere  to  be  found,  not  even  in  the 
serum  on  the  application  of  Gmelin's  very  delicate  test,  nor 
in  any  tissues  or  organs ;  there  was  no  icteric  discolora- 
tion anywhere.  On  the  other  hand,  if  in  pigeons  the  bile- 
ducts  only  were  ligatured,  bile  pigment  was  found  after  an 
hour  and  a  half  in  the  urine,  and  with  perfect  certainty  in' 
the  serum  after  five  hours.  It  follows,  from  these  valuable 
inquiries,  that  the  coloring  matter  of  bile  is  formed  in  the 
liver. 

The  same  applies  to  the  bile  acids.  This  has  already  been 
proved  by  an  inquiry  carried  out  by  FleischP  in  Ludwig's 
laboratory.  Bile  acids  cannot  be  shown  to  exist  in  normal 
blood.*  If  the  bile-duct  be  ligatured,  the  biliary  constituents 
pass  into  the  lymphatics  of  the  liver,  and  thence  direct  through 

1  Hans  Stern,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  lix.  p.  39 :  1885. 

~  Fowls,  ducks,  and  geese  continue  to  secrete  urine  after  the  liver  has  been 
ligatured  and  extirpated  (Minkowski  and  Naunyn,  Arch.  f.  exper.  Path.  u. 
Pharm.,  vol.  xxi.  p.  3:  1886). 

ä  E.  Fleischl,  Per.  d.  k.  sächs.  Ges.  d.  Wissensch.,  Math.-physikal.-Klasse, 
Sitzung  vom  8  Mai,  p.  42 :  1874.  Vide  also  Kuflferath,  Du  Bois'  Arch.,  p.  92  r 
1880,  and  V.  Ilarley,  ibid.,  p.  292  :  1893. 

*  We  must  however  assume  that  traces  of  bile  acids  do  occur  in  normal  blood, 
as  they  are  absorbed  from  the  intestine.  Dragendorff  (Zeitschr.  f.  anal.  Chem.y 
vol.  XI.  p.  4G7  :  1872)  and  Joh.  Hone  (Dissert.:  Dorpat,  1873)  found  traces  in 
normal  human  urine.  Hoppe-Seyler  and  L.  v.  Udranszki  dispute  this  statement 
(Zeilschr.  f.  physiol.  Chem.,  vol.  xii.  p.  375; 


BILE    PIGMENTS  337 

the  thoracic  duct  into  the  blood.  If,  after  ligaturing  the  bile- 
duct,  a  cannula  be  introduced  into  the  thoracic  duct  so  as  to 
collect  the  chyle,  bile  acids  may  be  shown  to  be  contained  in  it. 
If  the  bile-duct  and  the  thoracic  duct  be  ligatured  at  the  same 
time,  the  latter  becomes  distended  with  lymph,  but  no  trace  of 
bile  acids  can  be  found  in  the  blood. 

The  observations  of  Minkowski  and  Naunyn^  perfectly 
harmonize  with  the  results  obtained  by  Fleischl,  as  after  shut- 
ting out  the  liver  from  the  circulation,  they  were  never  able  to 
detect  bile  acids  in  the  blood. 

We  may  therefore  conclude  that  the  specific  constituents 
of  the  bile  acids  and  pigments  are  formed  in  the  liver. 

We  now  come  to  the  question  as  to  the  origin  of  the 
specific  biliary  constituents.  With  regard  to  the  bile  acids, 
their  nitrogenous  moieties,  glycocol  and  taurin,  are  doubtless 
derived,  as  I  have  already  shown  (pp.  177,  288),  from  proteid. 
Cholalic  acid,  which  is  non-nitrogenous,  does  not  necessarily 
originate  in  the  same  material.  It  is  conceivable  that  it  may 
be  derived  from  another  source,  and  subsequently  combine 
with  the  nitrogenous  compounds  by  a  process  of  synthesis, 
with  loss  of  water ;  this  would  be  entirely  analogous  to  the 
mode  of  formation  of  hippuric  acid.  We  should  note  the 
small  amount  of  hydrogen  contained  in  cholalic  acid  (p.  177). 
If  it  be  formed  from  fats  or  carbohydrates,  the  carbon 
atoms  of  the  molecule  must  become  linked  by  two  bonds  of 
affinity  instead  of  one,  as  in  the  case  of  these  two  classes. 
This  would  only  be  a  further  proof  that  syntheses  occurring  in 
the  animal  are  as  complicated  as  those  occurring  in  the  vege- 
table cell. 

The  coloring  matter  of  bile,  bilirubin  (vide  p.  323),  almost 
certainly  arises  from  the  coloring  matter  of  the  blood,  hematin. 
The  following  facts  support  this  view. 

Bile  pigments  are  found  only  in  animals  whose  blood  con- 
tains hemoglobin,  i.  e.,  the  vertebrata.  The  invertebrata  have 
not  hitherto  been  shown  to  possess  them.  It  might  be  objected 
that  this  depends  upon  some  other  peculiarity  of  the  vertebrata, 
as  blood-cells  containing  hemoglobin  are  not  the  sole  feature 
which  distinguishes  the  vertebrata  from  the  invertebrata. 
With  regard  to  this,  it  is  interesting  to  observe  that  the 
amphioxus,  which  has  no  red  blood-corpuscles,  but  Avhich  from 
its  whole  structure,  belongs  to  the  vertebrata,  forms  no  bile 
pigment.     Hoppe-Seyler  ^  has  searched  for  it  without  success. 

1  Minkowski  and  Naunyn,  Arch.  f.  exper.  Path.  u.  Pharm,  vol.  xxi.  p.  7  : 
1886. 

2  Hoppe-Seyler,  Pflüger's  Arch.,  vol.  xiv.  399 :  1877. 
22 


338  LECTURE    XXII 

It  is  well  known  that  the  liver  of  the  amphioxus  is  a  mere 
cecal  appendage  of  the  intestine,  the  gland  being  only  indi- 
cated as  in  the  embryos  of  the  higher  vertebrata. 

It  is  almost  certain  that  there  is  a  genetic  relation  between 
bile  pigments  and  hematin,  if  we  compare  their  constitution 
(compare  pp.  178,  323) — 

Hematin C32H3jN404Fe. 

Bilirubin C32H3gN40j. 

Biliverdin C32H36N4O8. 

Hematoporphyrin,  a  pigment  isomeric  with  bilirubin,  can 
be  artificially  prepared  from  hematin  by  treatment  with  hydro- 
bromic  acid.^ 

The  following  fact  may  also  be  brought  forward  as  an 
argument :  in  extravasations  of  blood  the  coloring  matter  of 
the  blood  disappears,  and  in  place  of  it  we  find  a  crystallized 
pigment,  which  Virchow^  was  the  first  to  examine  carefully, 
and  named  hematoidin.  The  same  writer  pointed  out  its 
resemblance  to  bile  pigment.  Subsequently  Robin,^  JaflFe,*  and 
Salkowski^  proved  the  identity  of  hematoidin  and  bilirubin. 
Langhans  ^  took  the  blood  from  the  vein  of  a  living  pigeon  and 
injected  it  under  the  skin  of  the  same  animal ;  after  two  or 
three  days  the  coloring  matter  of  the  blood  had  disappeared 
from  the  subcutaneous  clot,  and  was  replaced  by  bilirubin 
and  biliverdin.  Quincke  '^  performed  the  same  experiment  on 
dogs.  In  this  case  the  conversion  occupied  more  time  ;  the 
bilirubin  did  not  appear  in  the  subcutaneous  injection  before 
the  ninth  day.  Cordua^  injected  blood  into  the  abdominal 
cavity  of  dogs,  and  found  bilirubin  after  so  short  a  time  as 
thirty-six  hours.  Finally,  Recklinghausen  ^  has  seen  bile  pig- 
ment formed  in  the  blood  of  frogs  outside  the  body  after  from 
three  to  ten  days. 

Our  clinical  experience  entirely  accords  with  these  experi- 
ments upon  animals,  for  we  see  that  after  hemorrhages  under 

'  M.  Nencki  and  N.  Sieber,  Sitz.  d.  K.  Akad.  d.  Wissensch.  i.  Wien,  Math.- 
nat. -Klasse,  vol.  xcvii.  pt.  2:  1888. 

2  Virchow  in  his  Arch.,  vol.  i.  pp.  379,  407  :  1847. 

^  Robin,  Covipt.  rend.,  vol.  xli.  p.  506:  1855.  Robin  obtained  3  grms.  of 
hematoidin  crystals  from  an  hepatic  cyst,  and  analyzed  them. 

''Jaffe,  Virchow's  Arch.,  vol.  xxiii.  p.  192:  1862. 

^  E.  Salkowski,  Hoppe-Seyler's  Med.  chem.  Unters.,  Heft  iii.  p.  436  :  1868. 

^  Th.  Langhans,  Virchow's  Arch.,  vol.  xlix.  p.  66  :  1870. 

'  H.  Quincke,  Virchow's  Arch.,  vol.  xcv.  p.  125 :  1884. 

5  Herrn.  Cordua,  "  Ueber  den  Resorptiousmechanismus  von  Blutergüssen": 
Berlin,  Hirschwald,  1877. 

s  Recklinghausen,  "Handbh.  der  allgem.  Patholog.  d.  Kreislaufes  und  der 
Ernährung,"  p.  434:  Stuttgart,  Enke,  1883. 


BILE    PIGMENTS  339 

the  most  varied  conditions  (in  cerebral  hemorrhage,  in  pul- 
monary infarcts,  in  hematocele,  in  extravasations  depending 
upon  mechanical  injury,  in  abdominal  hemorrhages  consequent 
upon  extrauterine  pregnancy,  in  rupture  of  the  sac,  &c.), 
urobilin  [vide  p.  323)  the  product  of  the  conversion  of  bili- 
rubin occurs  in  large  quantities  in  the  urine.^ 

Bilirubin  is  sometimes  found  in  the  urine,  if  from  any 
cause  hemoglobin  passes  out  of  the  blood-corpuscles  into  the 
plasma.  This  may  be  brought  about  by  the  injection  of  water 
in  large  quantity,  of  chloroform,  ether,  or  glycerin  into  the 
blood,  or  merely  by  the  injection  of  a  solution  of  hemoglobin.^ 
It  may  however  be  questioned  whether  the  relation  is  as  simple 
as  it  appears,  and  whether  the  bile  pigment  occurring  in  the 
urine  is  formed  from  the  hemoglobin  that  has  passed  into  the 
plasma  within  the  circulation.  The  connection  is  probably  one 
of  an  indirect  character.^  The  presence  of  hemoglobin  in  the 
plasma  sometimes  causes  only  hemoglobinuria,  sometimes  both 
hemoglobinuria  and  bilirubinuria,  or,  again,  bilirubinuria  alone  ; 
sometimes  neither  of  these  occurs.  We  have  not  yet  satis- 
factorily settled  the  conditions  under  which  the  unaltered 
coloring  matter  of  blood  or  its  product  is  found  in  the 
urine. 

We  have  seen  that  bile  pigment  is  normally  formed  in  the 
liver,  but  the  observations  made  upon  extravasations  of  blood 
show  that  in  abnormal  conditions  it  may  also  arise  elsewhere. 
Hence  it  has  been  asked  whether  the  bile  pigment  occurring 
in  jaundice  is  invariably  formed  in  the  liver.  The  most  fre- 
quent cause  of  jaundice,  which  is  characterized  by  the  appear- 
ance of  bile  pigment  in  the  tissues  and  in  the  urine,  is  well 
known  to  be  a  narrowing  or  a  complete  occlusion  of  the  bile- 
ducts.  This  generally  occurs  at  the  orifice  of  the  common  bile- 
duct,  in  consequence  of  catarrh  of  the  duodenum,  or  from  the 
presence  of  biliary  calculi,  tumors,  and  the  like.  In  this  way 
the  bile  is  blocked  up,  and  reaches  the  lymphatics  of  the  liver, 
passes  into  the  blood  through  the  thoracic  duct,  and  thus  into 
all  the  tissues  and  the  urine.  We  term  this  form  obstructive, 
mechanical,  or  hepatogenous  jaundice.     In  contrast  to  this  an 

'  E.  von  Bergmann,  "  Die  Hirnverletzungen  mit  allgemeinen  und  mit  Herd- 
symptomen,"  in  E..  Volkmann's  Sammlung  klinischer  Vorträge,  No.  190  :  Leipzig, 
Breitkopf  and  Härtel,  1881 ;  B.  Dick,  Arch.  f.  Gynäkologie,  vol.  xxiii.  p.  1 : 
1884.  Comp,  also  G.  Hoppe-Seyler,  Virchow's  Arch.,  vol.  cxxiv.  p.  30  :  1891 ; 
and  vol.  cxxviii.  p.  43  :  1892. 

2  Kühne,  Virchow's  Arch.,  vol.  xiv.  p.  338:  1858.  M.  Hermann,  "De 
effectu  sanguinis  diluti  in  secretionem  urinae,"  Dissert,  inaug.:  Berolini,  1859. 
Nothnagel,  Berl.  klin.  Wochensch.,  p.  31 :  1866.  Tarchanoff,  Pflüger's  Arch., 
vol.  ix.  p.  53  :  1874. 

Vide  E.  Stadelmann,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xv.  p.  337 :  1882. 


340  LECTURE   XXII 

an  -  hepatogenous,  hematogenous,  or  chemical  jaundice  ^  has 
been  assumed,  which  was  attributed  to  a  conversion  of  the 
coloring  matter  of  blood  into  bile  pigment  outside  the  liver. 
A  case  was  assigned  to  the  latter  class  when  no  definite  lesions 
could  be  discovered  in  the  liver,  and  when,  the  flow  of  bile 
into  the  intestine  being  apparently  unchecked,  the  feces 
did  not  exhibit  the  "clay  color"  characteristic  of  jaundice 
(compare  p.  1 83) ;  moreover,  certain  forms  of  poisoning,  as 
from  arseniuretted  hydrogen,  chloroform,  ether,  fungi,  and  cer- 
tain severe  infective  diseases,  like  typhus,  malaria,  pyemia, 
gave  countenance  to  this  view.  In  many  of  these  cases  a 
passage  of  hemoglobin  from  the  blood-corpuscles  into  the 
plasma  could  be  directly  shown  under  the  microscope.  Stromata 
were  also  occasionally  found  in  the  blood,  and  hemoglobin  was 
seen  to  pass  into  the  urine.  It  was  therefore  considered  that 
in  these  cases  a  portion  of  the  hemoglobin,  which  had  passed 
into  the  plasma,  had  been  converted  into  bilirubin  outside  the 
liver. 

One  might  have  expected  to  be  able  to  distinguish  the  two 
forms  of  jaundice  by  the  passage  of  the  bile  acids  into  the 
urine  together  with  the  bile  pigments  in  obstructive  but  not  in 
hematogenous  jaundice.  But  it  is  manifest  that  the  bile  acids 
are  speedily  destroyed  after  their  passage  into  the  blood ; 
even  in  undoubted  obstructive  jaundice,  their  presence  in  the 
urine  can  sometimes  not  be  traced.  On  the  other  hand,  they 
are  sometimes  discovered  in  small  quantities  in  normal  urine 
(compare  p.  336,  note  4).  Large  quantities  of  bile  acids  in  the 
urine  certainly  allow  us  to  conclude  that  we  have  to  do 
with  obstructive  jaundice ;  but  their  absence  does  not  justify 
the  inference  that  we  have  to  deal  with  the  hematogenous 
form. 

More  recent  research  has  proved  that  there  is  not  at 
present  any  sound  basis  for  the  conclusion  that  the  bile 
pigment  occurring  in  jaundice  has  any  other  source  than  the 
liver. 

Minkowski  and  Naunyn^  removed  the  liver  of  a  goose, 
and  immediately  exposed  it,  as  well  as  a  healthy  goose,  to  the 
influence  of  arseniuretted  hydrogen.  After  half  an  hour,  the 
control  goose  evacuated  urine  containing  considerable  quantities 
of  biliverdin,  which    continued  to   be  secreted  for  two  days. 

1  H.  Quincke,  Virchow's  Arch.,  vol.  xcv.  p.  125 :  1884.  Minkowski  and 
Naunyn,  Arch.  f.  exp.  Path.  u.  Pharm.,  vol.  xxi.  p.  1 :  1886.  A  critical  account 
of  the  comprehensive  literature  on  the  various  forms  of  jaundice  is  given  by  these 
authors. 

2  Minkowski  and  Naunyn,  loc.  cit.,  p.  18.  Compare  also  Valentini,  Arch.  f. 
exper.  Path.  u.  Pharm.,  vol.  xxiv.  p.  412  :  1888. 


JAUNDICE  341 

On  the  other  hand,  the  urme  of  the  goose  without  the  liver 
at  first  showed  only  a  minute  quantity  of  biliverdin ;  but 
after  half  an  hour's  exposure  to  the  poison  hemoglobin  ap- 
peared in  the  urine,  and  the  urine  subsequently  discharged 
was  perfectly  free  from  bile  pigment.  The  blood  also  con- 
tained neither  bilirubin  nor  biliverdin.  It  is  therefore  ex- 
tremely probable  that  the  bile  pigment  appearing  in  the  urine 
after  poisoning  with  arseniuretted  hydrogen  has  its  source  in 
the  liver. 

According  to  my  view,  every  form  of  jaundice  is  induced 
by  obstruction.  We  must  not  forget  that  it  is  not  necessary 
that  the  larger  bile-ducts  should  be  completely  obstructed  in 
order  to  cause  the  passage  of  bile  into  the  blood.  The  slightest 
disturbance,  the  least  arrest  of  the  flow  from  the  primary  bile- 
ducts,  suffices  to  induce  it. 

So  long  as  there  is  an  unimpeded  flow  into  the  intestine, 
the  bile  pigment  follows  this  route,  and  does  not  pass  into 
the  urine.  Tarchanoff"  injected  a  solution  of  bile  pigment 
directly  into  the  blood  of  a  dog  with  a  biliary  fistula,  and 
found  an  increased  secretion  of  pigment  in  the  bile  which 
proceeded  from  the  fistula;  but  there  was  none  in  the  urine.^ 
We  may  therefore  assume  that  whenever  bile  pigment  occurs 
in  the  urine,  it  is  a  sign  of  biliary  obstruction.  The  bile  pig- 
ment which  is  formed  in  extravasations  of  blood  reappears  in 
the  urine,  as  already  said,  not  in  its  original  form,  but  re- 
duced to  urobilin.  We  need  not  be  surprised  at  such  a  reduc- 
tion taking  place  in  the  tissues,  as  we  know  from  the  researches 
of  Ehrlich  that  very  energetic  processes  of  reduction  occur  in 
many  organs  and  tissues.^  Ehrlich  injected  into  living  ani- 
mals blue  dye-stuffs,  as  alizarin  blue,  indophenol  blue,  which 
are  decolorized  by  the  withdrawal  of  oxygen.  These  dyes 
circulated  in  the  blood-plasma  without  being  altered.  But 
in  certain  tissues,  especially  in  the  connective  and  adipose 
tissues,  they  were  decolorized.  When  an  incision  was  made 
into  the  tissues,  they  at  first  appeared  colorless ;  the  blue 
color  did  not  appear  until  the  oxygen  of  the  air  had  ope- 
rated for  some  time.  Possibly  the  reducing  power  of  the 
tissues  explains  the  increased  excretion  of  urobilin  which 
accompanies  the  fading  of  jaundice.  The  bilirubin  which  had 
penetrated    the   tissues   during    the    biliary   obstruction   now 

^Tarchanoflf,  Pfliiger's  Arch.,  vol.  ix.  p.  332:  1874.  Adolf  Vossius  has  con- 
firmed these  results  by  fresh  experiments  {Arch.  f.  exper.  Path.  u.  Pharm.,  vol. 
xi.  p.  446:  1879).  Vide  also  A.  Kunkel,  Virchow's  Arch.,  vol.  Ixxix.  p  463- 
1880. 

2  P.  Ehrlich,  "  Das  Sauerstoflfbediirfniss  des  Organismus"  :  Berlin,  Hirsch- 
wald, 1885. 


342  LECTUEE    XXII 

returns  to  the  blood  as  urobilin,  and  passes  out  through  the 
kidneys  into  the  urine/ 

The  obstruction  of  the  bile  which  occurs  in  the  jaundice 
resulting  from  poisoning  by  arseniuretted  hydrogen  is  probably 
caused  in  the  following  manner.  There  is  an  increased  secre- 
tion of  bile,  for  the  intestine  in  the  poisoned  animals  is  loaded 
with  bile.  It  is  therefore  perfectly  plausible  to  assume  that 
the  copious  inspissated  bile  cannot  discharge  itself  quickly 
enough,  and  that  this  alone  suffices  to  induce  obstruction;^  for 
the  pressure  in  the  bile-ducts  is  very  slight,  and  can  be  over- 
come by  a  trifling  resistance.^  Stadelmann  ^  has  convincingly 
shown  that  the  jaundice  resulting  from  poisoning  by  arseni- 
uretted hydrogen  or  toluylendiamin  is  due  to  obstruction. 
When  dogs  with  biliary  fistulse  were  poisoned  with  these  sub- 
stances, there  was  a  great  increase  of  bile  in  the  secretion, 
which  was  moreover  very  thick  and  tenacious.  They  never 
found  catarrh  of  the  duodenum,  nor  occlusion  of  the  common 
bile-duct,  in  their  numerous  autopsies.  It  was  evident  that 
jaudice  resulting  from  the  action  of  toluylendiamin  was  due  to 
obstruction,  from  the  simple  fact  that  large  quantities  of  bile 
acids  were  found  in  the  urine.  In  the  jaundice  due  to  poison- 
ing by  arseniuretted  hydrogen,  large  amounts  of  bile  acids 
were  also  sometimes  met  with  in  the  urine. 

We  may  now  dismiss  the  subject  of  jaundice  and  the  forma- 
tion of  bile  pigments  in  the  liver.  We  possess  no  positive 
knowledge  as  to  the  fate  of  the  iron  which,  in  the  process  that 
we  have  been  discussing,  must  be  detached  from  the  hematin. 
In  the  liver  we  find  very  numerous  compounds  of  iron,  in  which 
the  iron  is  more  or  less  firmly  fixed ;  from  very  simple  inor- 
ganic forms,  such  as  oxid  and  phosphate  of  iron,  and  organic 
compounds  in  which  it  is  more  stable,  to  those  in  which  the 
iron  is  as  firmly  bound  as  in  hematin.^  We  know  nothing  as 
to  the  genetic  connection  of  these  compounds,  which  have 
scarcely  been  submitted  to  any  inquiry. 

As  already  mentioned,  the  formation  of  glycogen  is  one 
of  the  functions  of  the  liver.     The  reasons  why  we  are  compelled 

^  Vide  Kunkel,  loc.  cit.,  p.  463.     Compare  also  Quincke,  loc.  cit.,  p.  138. 

2  Minkowski  aud  Naunyn,  loc.  cit.,  p.  12. 

^  Heidenhain,  in  Hermann's  "Handb.  d.  Physiol.,"  vol.  v.  part  i.  p.  268 : 
Leipzig,  Vogel,  1883. 

■*  E.  Stadelmann,  Arch.  f.  exp.  Path.  u.  Pharm.,  vol.  xiv.  pp.  231,  422 : 
1881 ;  vol.  XV.  p.  337  :  1882 ;  vol.  xvi.  pp.  118,  221 :  1883.  Compare  also  Afanas- 
siew,  Zeitschr.  f.  Jdin.  3Ied.,  vol.  vi.  p.  281 :  1883. 

^  Vide  St.  Sz.  Zaleski,  Zeitschr.  f.  physiol.  Chem.,  vol.  x.  p.  453 :  1886,  where 
a  fall  account  of  the  literature  on  the  relations  of  iron  in  the  liver  is  given. 
Compare  also  the  interesting  illustrations  of  the  microscopical  preparations  in 
the  work  of  Minkowski  and  Naunyn,  loc.  cit. 


GLYCOGEN  343 

to  assume  that  the  sugar  which  passes  frcm  the  intestine  into 
the  portal  blood  is  deposited  in  the  liver  as  glycogen,  have 
already  been  given  (p.  188).  Glycogen  plays,  in  the  metab- 
olism of  animals,  a  part  similar  to  that  which  belongs  to 
starch  in  the  metabolism  of  plants  :  it  is  the  form  in  which 
the  excess  of  carbohydrates  is  stored  up  in  the  organism  for 
future  use. 

Glycogen  ^  is  distinguished  from  starch  by  its  property  of 
swelling  up  and  being  apparently  dissolved  in  cold  water.  The 
solution  is  however  never  clear,  but  opalescent  and  not  diffusible. 
Glycogen  therefore  in  this  respect  resembles  the  colloid  gummy 
carbohydrates,  dextrin,  arabin,  bassorin,  and  the  like ;  but  it  is 
more  complicated  than  dextrin,  as  this  is  obtained  by  the  de- 
composition of  glycogen.  It  yields  products  similar  to  those 
derived  from  starch  when  broken  up,  and  is  probably  of  as  com- 
plex a  nature. 

There  is  no  room  for  the  storage  of  the  whole  excess  of 
carbohydrates  in  the  liver.  The  liver  of  mammals  rarely  yields 
as  much  as  10  per  cent,  of  glycogen,  and  generally  much  less. 
The  human  liver  therefore,  which  weighs  1500  grms.,  con- 
tains at  most  150  grms.  of  glycogen.  After  a  meal  in  which 
carbohydrates  have  been  copiously  consumed,  much  larger 
quantities  often  pass  into  the  portal  vein  within  a  few  hours, 
and  we  must  bear  in  mind  that  at  the  commencement  of  a 
meal  the  liver  contains  some  glycogen.  It  only  becomes 
perfectly  free  from  glycogen  after  several  weeks'  starvation. 
A  large  portion  of  the  sugar,  derived  from  the  intestine,  must 
therefore  pass  through  the  liver.  But  as  the  amount  of  sugar 
in  the  blood  does  not  rise  after  a  diet  rich  in  that  substance, 
the  sugar  must  be  deposited  in  other  organs  than  the  liver. 
We  do,  in  fact,  know  that  the  muscles  contain  glycogen.^  The 
percentage  amount  of  this  carbohydrate  in  the  muscles  is  much 

Cl.  Bernard  {Gas.  med.  de  Paris,  No.  13  :  1857;  Compt.  rend.,  vol.  iliv. 
p.  578:  1857)  and  V.  Hensen  (Virchow's  Arch.,  vol.  xi.  p.  395:  1857)  each  dis- 
covered glycogen  independently  of  the  other,  and  isolated  it  from  the  liver. 
Brücke  [Sitsungsber.  d.  Wien.  Akad.,  vol.  Ixiii.  part  2,  p.  214  :  1871)  has  shown 
a  method  for  the  quantitative  estimate  of  glycogen.  Vide  also  O.  Nasse,  Pflüger's 
Arch.,  vol.  xxiv.  pp.  1-114:  1881:  R.  Böhm  and  Fr.  A.  Hofmann,  Arch.  f. 
exper.  Path.  u.  Pharm.,  vol.  vii.  p.  489:  1877;  vol.  viii.  pp.  271,  375:  1878; 
vol.  X.  p.  12  :  1879  ;  Pflüger's  Arch.,  vol.  xxiii.  pp.  44,  205  :  1880.  Compare  also 
Külz,  Pflüger's  Arch.,  vol.  xxiv.  pp.  1-114 :  1881,  for  a  complete  account  of  the 
literature  on  the  subject. 

^  The  occurrence  of  glycogen  in  the  muscles  was  discovered  by  Bernard 
{Compt.  rend.,  vol.  xlviii.  p.  683  :  1859)  and  by  O.  Nasse  (Pflüger's ^rcA.,  vol.  ii. 
p.  97:  1869;  and  vol.  xiv.  p.  482:  1877).  A  summary  of  the  first  accounts  of 
glycogen  in  muscle  is  given  by  E.  Külz,  loc.  cit.,  p.  42.  Glycogen  in  small 
quantities  is  also  present  in  other  organs.  Compare  M.  Abeles,  Centralbl.  f.  d. 
med.  Wiss.,  p.  449  :  1885. 


344  LECTURE    XXII 

smaller  than  that  in  the  liver,  and  seems  to  vary  in  different 
animals ;  the  muscles  at  the  most  contain  1  per  cent.,  generally 
less  than  ^  per  cent.  Böhm  ^  found  the  absolute  quantity 
contained  in  the  muscles  of  the  cat  nearly  as  large  as  that  in 
the  liver.  The  muscles  of  a  horse,  after  nine  days'  starvation, 
still  contained  from  1  to  2.4  per  cent,  glycogen.^  As  we  shall 
see  directly,  glycogen  is  the  material  of  muscular  work.  It 
disappears  entirely  from  the  muscles  and  liver  after  fatigue 
and  want  of  food ;  ^  and  sooner  from  the  liver  than  the 
muscles.*  It  may  be  taken  as  a  fact  that  when  there  is  an 
insufficient  supply  of  food  the  organs  which  are  at  rest  give 
up  their  store  of  glycogen  to  those  that  are  working. 

It  is  probable  that  glycogen  is  conveyed  from  one  part  of 
the  system  to  another  in  the  form  of  grape-sugar.  When 
broken  up  by  ferments,  glycogen  is  converted,  m  the  first 
instance,  into  a  carbohydrate  resembling  dextrin,  and  into  a 
variety  of  sugar  resembling  maltose.^  But  in  the  living 
body,  the  passage  of  the  glycogen  from  the  tissues  into 
the  blood  causes  a  further  advance  in  this  change,  and  the 
glycogen  is  as  completely  converted  into  molecules  of  grape- 
sugar  as  it  would  be  by  boiling  with  dilute  sulphuric  acid. 
The  majority  of  inquirers  have  been  unable  to  show  the 
presence  of  glycogen  or  of  any  colloid  carbohydrates  in  the 
blood.^ 

Glycogen  is  not  only  a  source  of  power  for  the  muscles ;  it 
is  likewise  a  source  of  heat.  If  we  lower  the  temperature  of 
a  rabbit  by  cold  baths  and  cold  air,  all  but  minute  traces  of 
the  glycogen  is  found  to  have  disappeared  from  the  liver  after 
a  few  hours,''  Starvation  deprives  warm-blooded  animals  more 
rapidly  of  their  glycogen  than  cold-blooded  animals,  and  among 

1  R.  Böhm,  Pfliiger's  Arch.,  vol.  xxiii.  p.  51 :  1880. 

2  G.  Aldehoflf  (Kiilz's  lahoraXotj) ,  Zeitschr.  f.  Biolog.,  vol.  xxv.  p.  162 :  1888. 
^  B.  Luchsinger,  "  Experimentelle  und  kritische  Beiträge  zur  Physiologie 

und  Pathologie  des  Glycogens,"  Vierteljahrschr.  der  Züricher  naturforschenden 
Gesellschaft :  1875.  See  also  Pfliiger's  Arch.,  vol.  xviii.  p.  472  :  1878.  G. 
Aldehoff,  Zeitschr.  f.  Biolog.,  vol.  xxv.  p.  137  :  1889. 

*  Aldehoff",  loc.  dt. 

^  O.  Nasse,  Pfliiger's  Arch.,  vol.  xiv.  p.  478  :  1877  :  Musculus  and  von 
Mering,  Zeitschr.  f.  physiol.  Chem.,  vol.  ii.  p.  413  :  1878  ;  E.  Külz,  loc.  cit., 
pp.  52-57  and  81-84. 

®  O.  Nasse,  "  De  materiis  amylaceis,  num  in  sanguine  animalium  inveniantur, 
disquisitio,"  Dissert.:  Halle,  1866:  Hoppe-Seyler.  "Physiol.  Chem.,"  p.  406  : 
Berlin,  1881.  Salomon  comes  to  different  conclusions  {Deutsche  med.  Wochenschr., 
No.  35  :  1877).  Frerichs  ("  Ueb.  d.  Diabetes,"  p.  6  :  Berlin,  1884)  also  comes  to 
the  conclusion  that  there  is  constantly  a  small  amount  of  glycogen  in  the  blood, 
for  the  most  part  contained  in  the  white  blood-corpuscles.  This  however  is  not 
a  peculiarity  of  leucocytes,  but  is  probably  common  to  all  cells. 

■^  E.  Külz,  Pfliiger's  Arch.,  vol.  xxiv.  p.  46  :  1881.  Vide  also  Böhm  and 
Hoflfmann,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  viii.  p.  295  :  1878. 


GLYCOGEN  345 

the  former  small  animals  with  a  relatively  large  surface  lose 
it  sooner  than  the  bigger  ones.^  Starving  rabbits  lose  their 
glycogen  in  from  four  to  eight  days ;  dogs  not  before  two  or 
three  weeks  ;  frogs,  in  summer,  after  from  three  to  six  weeks. 
Frogs  which  have  had  no  food  during  the  whole  winter  do  not 
show  an  entire  absence  of  glycogen  until  the  spring.  Hiber- 
nating mammals  are  equally  slow  in  consuming  their  store  of 
glycogen.^ 

If  we  introduce  carbohydrates  into  the  stomach,  or  directly 
into  the  blood  of  rabbits,  whose  liver,  after  six  days  of 
starvation,  has  been  rendered  quite  free  from  glycogen,  a 
large  amount  of  glycogen  is  found  in  the  liver  after  a  few 
hours.^ 

It  is  probable  that  the  glycogen  stored  in  the  liver  and  the 
muscles  is  not  derived  exclusively  from  the  carbohydrates  of 
the  food.  It  appears  that  the  albuminous  and  gelatinous  sub- 
stances of  the  food  also  take  part  in  the  formation  of  glycogen. 
Animals  that  have  been  exclusively  fed  for  a  considerable 
period  on  lean  meat,  exhibit  large  stores  of  glycogen  in  their 
liver  and  muscles.  Naunyn  *  fed  fowls  for  a  long  time  (in  one 
experiment  for  six  weeks)  exclusively  on  muscle,  which  had 
been  stewed  down  and  squeezed  out,  and  therefore  was  almost 
entirely  free  from  carbohydrates ;  and  he  then  found  large 
quantities  of  glycogen  (as  much  as  3.5  per  cent.)  in  the 
liver.  Von  Mering^  fed  a  dog,  which  had  been  previously 
starved  for  twenty-one  days,  for  four  days  exclusively  on 
washed  bullock's  fibrin.  The  animal  was  killed  six  hours  after 
it  had  been  last  fed,  and  the  liver,  which  weighed  540  grms. 
contained  16.3  grm.  of  glycogen.  A  control  animal  of  nearly 
the  same  size  showed,  after  twenty-one  days  of  starvation, 
0.48  grm.  of  glycogen  in  the  liver.  It  would  necessitate  very 
forced  modes  of  explanation  to  assume  from  these  and  many 
other  similar  experiments  that  the  glycogen  did  not  arise  from 
the  proteid. 

We  may  also  quote,  in  support  of  the  view  that  carbo- 

''■  B.  Luchsinger,  loc.  cit. 

2  Schiff,  "  Unt.  ueber  die  Zuckerbildung  in  der  Leber,"  p.  30:  Würzburg, 
1859;  Valentine,  Moleschott's  Unters,  zur  Naturlehre,  &c.,  vol.  iii.  p.  223:  1857; 
C.  Aeby,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  iii.  p.  184:  1875 ;  Voit,  Zeitschr. 
f.  Biolog.,  vol.  xiv.  p.  118  :  1878. 

^  E.  Kiilz,  Pflüger's  Arch.,  vol.  xxiv.  pp.  1-19 :  1881.  The  numerous  experi- 
ments of  a  similar  nature  made  by  earlier  authors  are  given  here. 

*  B.  Naunyn,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  iii.  p.  94 :  1875. 

s  Von  Mering,  Pflüger's  Arch.,  vol.  xiv.  p.  282  :  1877.  The  experiments 
made  on  this  subject  by  earlier  authors  are  appended.  Vide  also  Benj.  Finn, 
Verhandl.  d.  physik.  med.  Ges.  zu  Würzburg,  N.F.,  vol.  xi.  Heft  i.,  ii. :  1876; 
and  S.  Wolfiberg,  Zeitschr.  f.  Biolog.,  vol.  xii.  p.  310  (Exp.  4):  1876. 


346  LECTUEE   XXII 

hydrates  are  formed  from  proteid,  the  fact  that  in  the  severe 
form  of  diabetes  mellitus,  under  a  protracted  and  exclusive 
flesh-diet,  the  secretion  of  sugar  does  not  cease,  and  that  the 
quantity  of  sugar  increases  in  proportion  to  the  amount  of 
proteid  consumed.^ 

Von  Mering's  experiments  on  phloridzin  diabetes  are  well 
worth  mentioning.^  Phloridzin  is  a  glucosid  found  in  the 
root  cortex  of  apple  and  cherry  trees.  If  we  administer  a 
certain  amount  of  this  to  a  dog  (1  grm.  per  kilo,  body-weight) 
we  find,  after  a  few  hours,  sugar  in  the  urine.  This  glycosuria 
ceases  in  two  or  three  days,  and  we  then  find  the  liver  and 
muscles  totally  free  from  glycogen.  If  we  now  give  another 
dose  of  phloridzin,  we  again  find  a  large  amount  of  sugar  ex- 
creted. Von  Mering  concludes  that  this  must  be  derived  from 
proteid.  We  must  however  acknowledge  the  possibility  that 
this  sugar  may  arise  from  fats.  I  have  already  (Lecture  XIII.) 
noted  certain  fats  which  point  to  a  conversion  of  fat  into 
sugar,  and  would  cite  especially  the  constant  percentage  of 
sugar  in  the  blood  of  starving  animals  which  have  long  used 
up  their  store  of  glycogen,  and  sparing  their  proteid  as  much 
as  possible,  are  living  mainly  at  the  expense  of  their  fat.  A 
conversion  of  fat  into  sugar  has  long  been  familiar  to  the 
vegetable  physiologist.  Certain  seeds  contain  no  starch,  the 
place  of  this  substance  being  taken  by  fat.  If  such  seeds  are 
allowed  to  germinate  in  the  dark  in  order  to  prevent  the 
formation  of  new  organic  substances,  the  fat  is  seen  to  dis- 
appear from  the  cotyledons  and  is  replaced  by  starch,  gum, 
sugar  and  cellulose.^  If  starchy  seeds  germinate  in  a  glass 
tube  over  mercury  no  alteration  occurs  in  the  volume  of  the 
air  in  the  tube.  If  oily  seeds  are  placed  under  the  same 
conditions,  the  mercury  rises  in  the  tube,  since  oxygen  is 
used  up  in  the  transformation  of  fats  into  carbohydrates.*  J. 
Seegen  is  of  opinion  that  a  similar  conversion  of  fat  into 
carbohydrate  occurs  in  the  liver  of  the  mammal,  and  bases  his 
argument  on  the  following  experiment.  Pieces  of  liver  from  a 
freshly  killed  animal  are  weighed,  cut  up  finely,  and  allowed  to 
stand  with  defibrinated  blood  at  the  body  temperature.    To  one 

1  Von  Mering,  "  Tageblatt  der  49  Naturforscherversammlung  in  Hamburg," 
summarized  in  the  Deutsche  Zeilschr.f.  prakt.  Med.,  No.  40:  1876;  and  No. 
18:  1877;  Kiilz,  Arch,  f.  exper.  Path.  u.  Pharm.,  vol.  vi.  p.  140:  1876. 

2  Von  Meriug,  Verhandl.  d.  Congr.  f.  inn.  Medicin.,  Fünfter  Congress,  Wies- 
baden, p.  185 :  1886  ;  and  Sechster  Congress,  Wiesbaden,  p.  349  :  1887. 

^  Sachs,  Potan.  Zeit.:  1859;  Peters,  "Landw.  Versuchsstationen,"  vol.  iii.: 
1861. 

*  An  experiment  by  Wiesner,  described  by  Seegen  in  "  Die  Zuckerbildung  im 
Thierkörper,"  &c.,  p.  155:  Berlin,  1890. 


GLYCOGEN  347 

portion  of  this  mixture  a  fine  emulsion  of  fat  is  added.  Air  is 
then  allowed  to  bubble  through  the  mixtures  for  five  to  six 
hours.  At  the  end  of  this  time  the  amount  of  sugar  is 
determined  in  the  mixtures,  and  is  found  to  be  always  higher 
in  the  liver  to  which  fat  has  been  added.  Seegen  concludes 
that  fat  is  converted  in  the  liver  into  sugar.  In  harmony  with 
this  assumption  is  the  fact  that  the  blood  of  the  hepatic  veins 
is  almost  free  from  oxygen,  whereas  the  blood  flowing  from 
other  organs  always  contains  considerable  quantities  of  this  gas. 

We  must  conclude  therefore  that  as  soon  as  the  amount  of 
sugar  in  the  blood  sinks  below  normal,  the  liver  pours  into  the 
blood  sugar  which  may  be  derived  not  only  from  glycogen  and 
proteid,  but  also  from  fats.  Whether  the  other  organs  can  also 
convert  their  fat  into  sugar,  or  whether  the  fat  must  be  first 
transported  to  the  liver  in  order  to  effect  this  conversion  cannot 
as  yet  be  determined. 

Many  attempts  have  been  made  to  decide  by  experiment 
whether  glycogen  arises  from  the  fatty  materials  of  food. 
Almost  all  authors  ^  agree  that  the  glycogen  of  the  liver  does 
not  increase  in  amount  after  fatty  food. 

*  A  summary  of  these  authors  is  given  by  Von  Mering,  Pflüger 's  Arch.,  vol. 
xiv.  p.  282  :  1877. 


LECTURE  XXIII 

THE   SOURCE   OF   MUSCULAR    ENERGY 

In  our  last  observations  on  the  formation  of  glycogen  and 
the  behavior  of  carbohydrates  in  the  body,  I  repeatedly  stated 
that  glycogen  must  be  regarded  as  the  material  of  muscular 
work.  We  will  now  proceed  to  consider  the  facts  which 
have  led  to  this  view,  and  to  give  a  connected  account  of 
all  that  is  at  present  known  concerning  the  source  of  muscular 
energy. 

The  most  obvious  theory  that  the  source  of  muscular  work 
is  the  metabolism  of  those  substances  which  form  the  main 
constituents  of  muscle,  viz.,  proteids,  was  obstinately  main- 
tained by  Liebig  ^  to  the  end  of  his  life.  This  teaching  was 
however  shown  to  be  erroneous  by  the  following  experi- 
ment : — 

Fick  and  Wislicenus,  from  the  Lake  of  Brienz,^  ascended 
the  Faulhorn,  the  summit  of  which  is  1956  meters  above  the 
level  of  the  lake.  The  urine  excreted  during  the  six  hours' 
ascent  and  for  the  succeeding  six  hours  was  collected,  and  the 
nitrogen  contained  in  it  was  estimated.  During  this  time,  and 
for  twelve  hours  previous  to  the  commencement  of  the  experi- 
ment, only  non-nitrogenous  food,  starch,  fat,  and  sugar,  had  been 
taken.  The  consumption  of  proteid  was  calculated  from  the 
nitrogen  found  in  the  urine.  In  Fick  it  amounted  to  38,  and 
in  Wislicenus  to  37  grms.  From  the  amount  of  heat  produced 
by  the  combustion  of  the  carbon  and  hydrogen  in  the  proteid,  a 
maximal  value  ^  was   deduced  for  the  heat-equivalent  of  the 

^  It  is  very  instructive  to  read  the  original  works  in  which  the  reasons 
adduced  in  favor  of  and  against  Liebig's  doctrine  are  given.  To  this  end  we 
recommend  Liebig's  treatise,  "  Ueber  die  Gährung  und  die  Quelle  der  Muskel- 
kraft und  über  Ernährung ;  "  Liebig's  Ann.  d.  Chem.  u.  Pharm.,  vol.  cliii.  pp.  1 
and  157 ;  and  Voit's  reply,  "  Ueber  die  Entwickelung  der  Lehre  von  der 
Quelle  der  Muskelkraft  und  einiger  Theile  der  Ernährung  seit  25  Jahren," 
Zeitschr.f.  Biolog. ,  vol.  vi.  p.  305  :  1870.  The  older  literature  on  this  question 
is  here  critically  treated. 

2  A.  Fick  and  J.  Wislicenus,  Vierteljahr  sehr,  der  Züricher  naturforschenden 
Ges.,  vol.  X.  p.  317:  1865. 

3  That  this  value  must  be  much  too  high  is  evident  from  what  we  have  men- 
tioned before  (p.  61  et  seq.). 

348 


THE    SOURCE    OF    MUSCULAR    ENERGY  349 

proteid,  and  it  was  found  that  37  grms.  of  proteid  yielded  250 
units  of  heat,  which  corresponds  to  106,000  kilogram  meters  of 
work.  Wislicenus  weighed  76  kgrms.  It  follows  that,  in 
merely  raising  his  body  to  the  summit  of  the  mountain,  he  had 
done  work  amounting  to  76  x  1956  =  148,656  kilogrammeters. 
But  the  work  done  during  the  ascent  was  really  much  greater ; 
Fick  and  Wislicenus  calculated  that  the  work  done  by  the 
heart  and  by  respiration  in  the  same  time  amounted  to  30,000 
kilogrammeters.  We  have  also  to  consider  that  even  on  level 
ground  every  step  entails  work,  which  is  converted  into  heat 
and  is  lost,  and  that  the  other  parts  of  the  body,  the  head  and 
arms,  are  moved  during  the  ascent,  etc.  It  follows  that  much 
more  work  had  been  done  than  would  be  covered  by  the 
potential  energy  contained  in  the  proteid  consumed.  The  non- 
nitrogenous  constituents  of  the  food  and  of  the  body  must 
therefore  have  been  utilized  as  sources  of  energy. 

The  view  that  proteid  is  the  exclusive  working  material  of 
muscle  is  more  precisely  controverted  by  a  series  of  very  care- 
ful experiments  on  metabolism.  These  show  that  the  excretion 
of  nitrogen  during  twenty-four  hours  of  extreme  labor  is  as 
great  as,  or  but  little  more  than,  the  quantity  excreted  during 
rest ;  but  that,  on  the  other  hand,  the  excretion  of  carbonic 
acid  and  the  absorption  of  oxygen  is  much  increased  on  the 
days  of  work,  and  that  therefore  during  muscular  work  non- 
nitrogenous  food  is  chiefly  consumed. 

Voit  ^  was  the  first  to  carry  out  a  careful  experiment  of  this 
kind.  He  caused  dogs  to  run  in  a  large  tread-mill.  On  the 
days  before  and  after  the  day  of  work,  the  animals  were 
quiescent  with  the  same  food.  Some  of  the  experiments  were 
made  on  fasting  animals.  The  output  of  nitrogen  for  twenty- 
four  hours  was  accurately  determined,  and  it  resulted,  from  two 
experiments  with  fasting  animals,  that  the  excretion  of  nitrogen 
was  not  increased  on  the  working  days.  In  two  other  experi- 
ments with  a  fasting  animal,  and  in  two  with  a  diet  of  lean 
meat,  the  increase  was  very  slight. 

More  recently,  O.  Kellner^  has  instituted  similar  experi- 
ments on  horses  at  the  experimental  farm  of  Hohenheim.  On 
the  working  days,  he  found  a  greater  increase  in  the  excretion 
of  nitrogen  than  was  shown  in  the  experiments  of  Voit.  It 
was  only  when  very  large  quantities  of  carbohydrates  were 
given  to  the  horses  that  this  increase  failed. 

1  C.  Voit,  "Unt  über  den  Einfluss  des  Kochsalzes,  des  Kaffees  und  der 
Muskelbewegungen  auf  den  Stoffwechsel,"  p.  153,  et  seq.:  München,  1860;  and 
Zeitschr.  f.  Biolog.,  vol.  ii.  p.  339 :  1866. 

-  O.  Kellner,  Landwirthshaftliche  Jahrbücher,  vol.  viii.  p.  701 :  1879 ;  and 
vol.  ix.  p.  651 :  1880. 


350  LECTURE    XXIII 

Pettenkofer  and  Voit  ^  have  also  made  experiments  on  man 
to  determine  the  influence  of  work  upon  the  excretion  of  nitro- 
gen. The  elimination  of  carbonic  acid,  and  indirectly  the 
amount  of  oxygen  consumed,  was  determined  at  the  same  time 
by  the  respiratory  apparatus.  They  foimd  that  on  the  working 
days  the  excretion  of  nitrogen  was  identical  with  that  on  the 
days  of  rest,  the  food  being  the  same.  The  amount  of  sul- 
phuric and  phosphoric  acids  secreted  was  not  increased  on  the 
working  days,  but  the  excretion  of  carbonic  acid  and  the 
absorption  of  oxygen  rose  very  considerably. 

Lavoisier^  had  already  shown  that  the  absorption  of 
oxygen  and  the  excretion  of  carbonic  acid  were  increased 
by  muscular  work.  Vierordt,^  Scharling,*  Ed.  Smith,^  C. 
Speck,^  and  others,  using  more  perfect  methods,  have  confirmed 
this  discovery.  The  increase  in  the  absorption  of  oxygen  and 
in  the  excretion  of  carbonic  acid  has  been  determined  not  only 
by  the  investigation  of  the  interchange  of  gases  in  the  respira- 
tory apparatus,  but  also  by  a  comparative  determination  of  the 
oxygen  and  the  carbonic  acid  in  venous  blood,  taken  from  the 
quiescent  and  the  tetanized  muscle.  This  was  done  by  Ludwig 
and  Sczelkow,^  and  finally  in  a  masterly  inquiry  carried  out  in 
Ludwig's  laboratory  by  Max  von  Frey,*  with  the  advantage  of 
all  the  improved  technical  aids. 

From  the  experiments  that  have  been  quoted,  it  is  apparent 
that  muscle  chiefly  works  with  non-nitrogenous  food,  and  carbo- 
hydrates readily  suggest  themselves,  as  they  are  invariably 
stored  up  in  muscle  in  the  form  of  glycogen.  CI.  Bernard,  the 
discoverer  of  glycogen,  was  also  the  first  to  observe  that  this 
store  of  glycogen  disappears  during  work.^     He  also  found  that 

1  Pettenkofer  and  Voit,  Zeitschr.  f.  Biolog.,  vol.  ii.  pp.  488-500  :  1866.  Com- 
pare also  Felix  Schenk,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  ii.  p.  21 :  1874 ;  and 
Oppenheim,  Pflüger's  ^rcA.,  vol.  xxiii.  p.  484:  1880. 

*  Seguin  and  Lavoisier,  "  Premier  memoire  sur  la  respiration  des  animaux," 
Mem.  de  I' Acad,  des  Sciences,  p.  185 :  1789 ;  CEuvres  de  Lavoisier,  Paris,  Im- 
primerie  imperiale,  vol.  ii.  pp.  688,  696 :  1862 ;  and  Lavoisier's  letter  to  Black, 
dated  November  19,  1790,  printed  in  the  "Ptcportof  the  Forty-first  Meeting  of 
the  British  Assoc,  for  the  Adv.  of  Science,"  held  at  Edinburgh,  in  August,  1871, 
p.  191 :   London,  1872. 

^  Vierordt,  "  Physiologie  des  Athmens  "  :    Karlsruhe,  1845. 

■*  Scharling,  Ann.  d.  Chem.  u.  Pharm.,  vol.  xlv.  p.  214  :  1843  :  Journ.  f.  prakt. 
Chem.,  vol.  xlviii.  p.  435  :  1849. 

sEd.  Smith,  Phil.  Trans.,  vol.  cxlix.  (2)  pp.  681,  715:  1859;  Medico- 
chirurg.  Trans.,  vol.  xlii.  p.  91 :  1859. 

*  C.  Speck,  Schriften  der  Ges.  zur  Beförderung  d.  get.  Naturioissensch.  zu 
Marbiirg,  vol.  x.:  1871 ;  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  ii.  p.  405 :  1874. 

'  Ludwig  and  Sczelkow,  Wiener  Sitzungsher., -vol. -sly.  t?. 171 :  1862;  Zeitschr. 
f.  rat.  3fed.,  vol.  xvii.  p.  106 :   1862. 

»  Max  von  Frey,  Du  Bois'  Arch.,  pp.  519,  533 :  1885. 
9  CI.  Bernard,  Compt.  rend.,  vol.  xlviii.  p.  683  :  1859. 


THE   SOURCE   OF   MUSCULAR    ENERGY  351 

when  a  muscle  is  artificially  brought  to  a  state  of  quiescence 
by  division  of  its  nerve,  its  glycogen  increases.  These  state- 
ments of  Bernard  have  been  subsequently  confirmed  by  many 
experiments.^  If  one  of  the  hind  legs  of  a  frog  be  tetanized, 
it  is  always  found  to  contain  less  glycogen  than  the  other, 
which  has  been  at  rest. 

Külz^  allowed  dogs  that  had  been  previously  well  fed  to 
starve  for  one  day,  and  on  this  day  to  drag  a  heavy  cart  for 
from  five  to  seven  hours.  The  dog  was  then  immediately  killed, 
and  the  amount  of  glycogen  in  his  liver  determined.  Of  five 
dogs  employed  in  this  experiment,  the  liver  in  four  showed  that 
all  but  mere  traces  of  glycogen  had  disappeared.  The  liver  of 
the  fifth,  which  was  distinguished  from  the  others  by  being  old, 
very  fat  and  sluggish,  weighed  240  grms.,  and  contained  0.8 
grm.  of  glycogen.  I  have  previously  remarked  that  during 
starvation  without  work  glycogen  does  not  disappear  from  the 
liver  of  a  dog  until  the  third  week  (pp.  344-345). 

Hence  there  can  be  no  doubt  that  carbohydrates  serve  as  a 
source  of  muscular  energy. 

However,  it  would  be  too  much  to  assume  that  carbo- 
hydrates are  the  sole  source  of  muscular  energy.  We  have 
just  become  acquainted  with  experiments  from  which  it  appears 
very  probable  that  glycogen  is  formed  from  proteid  (p.  345). 
Hence  we  infer  that  proteid  may  also  serve  as  a  source  of 
muscular  energy.  It  is  a  fact  that  Carnivora  may  be  fed  for 
a  long  time  exclusively  on  lean  meat,  without  impairing  mus- 
cular vigor.  I  cannot  conceive  any  explanation  of  the  metab- 
olism of  the  animals  thus  fed,  without  assuming  that  proteid 
may  serve  as  a  source  of  muscular  power. 

Nor  is  it  improbable  that  fat  may  serve  for  the  same 
purpose.  It  would  not  be  difficult  to  determine  this  question 
by  experiments  upon  fasting  dogs.  Külz  has  already  shown 
that  a  fasting  dog  consumes  its  store  of  glycogen  on  the  very 
first  day  of  hard  work.  A  determination  of  the  excretion  of 
nitrogen  and  carbon  on  subsequent  days,  when  the  work  was 
continued,  would  afford  a  certain  reply  to  the  question  whether 
chiefly  proteid  or  chiefly  fat  supplies  the  animal  with  working 
power.  When  Voit  made  his  experiments  on  fasting  dogs,  the 
animal  generally  worked  only  one  day  ;  in  one  of  his  experi- 
ments ^  however,  the  work  was  continued  for  three  successive 
days,  and  they  had  been  preceded  by  three  fasting  days  with- 

1  An  account  of  these  is  given  by  E.  Kiilz,  Pfliiger's  Arch.,  vol.  xxiv.  p.  42  : 
1881 ;  and  Ed.  Marche,  Zeitschr.  f.  Biolog.,  vol.  xxv.  p.  163  :  1889. 

2  E.  Kiilz,  loc.  cit.,  p.  45. 

3  Voit,  "  Ueb.  d.  Einfl.  d.  Kochsalzes,"  &c.,  pp.  157,  158. 


352  LECTURE   XXIII 

out  work.  Kiilz's  dogs  worked  and  fasted  for  one  day  only, 
previous  to  which  they  had  been  supplied  with  ample  food  for 
some  days,  and  still  after  the  first  day  of  work  their  glycogen 
had  disappeared.  It  follows  therefore  that  Voit's  dog  must 
have  been  quite  free  from  glycogen  on  the  second  and  third 
days  of  hunger  and  work.  Nevertheless  there  was  only  a 
trifling  increase  in  the  excretion  of  urea.  I  think  therefore 
it  must  be  concluded  from  this  experiment  that  the  store  of 
fat  in  this  dog  had  been  drawn  upon  to  carry  on  its  muscular 
work. 

I  hold  that  muscle  draws  its  energy  from  all  the  three 
main  classes  of  food-stuffs.  We  might  assume  ä  priori,  on 
teleological  grounds,  that  in  the  performance  of  its  most 
important  functions,  the  organism  is  to  a  certain  extent 
independent  of  the  quality  of  its  food.  As  long  as  non- 
nitrogenous  food  is  supplied  in  adequate  quantity  or  is  stored 
up  in  the  tissues,  muscular  work  is  chiefly  maintained  from 
this  store.  When  it  is  gone  the  proteids  are  attacked.  The 
results  obtained  from  the  above-mentioned  experiments  of 
Kellner  entirely  agree  with  this  statement ;  he  found  that,  in 
the  horse,  the  excretion  of  nitrogen  is  increased  by  muscular 
work  only  when  the  animal  does  not  receive  a  sufficient  supply 
of  carbohydrates. 

It  has  often  been  surmised  that  muscular  energy  is  not 
derived  from  the  processes  of  oxidation,  but  from  those  of  de- 
composition. Certain  facts  seemed  to  favor  this  view.  Thus 
Hermann  ^  found  that  an  excised  muscle  contains  no  removable 
oxygen,  and  that  nevertheless  it  executes  numerous  contractions 
and  gives  off  carbonic  acid  when  placed  in  a  medium  de- 
prived of  all  oxygen.  We  know  that  the  chemical  potential 
energy  introduced  by  food  may  in  part  be  converted,  by  mere 
breaking  up  without  oxidation,  into  kinetic  energy ;  that  the 
heat  of  combustion  of  decomposition  products  is  lower  than 
that  of  the  original  food-stuffs,  and  that  therefore  heat  must 
be  liberated  during  decomposition.  We  have  given  direct 
proof  that  this  development  of  heat  accompanies  many  proc- 
esses of  decomposition.     (Compare  pp.  64,  153.) 

The  above-mentioned  fact,  that  in  muscular  work  the 
consumption  of  oxygen  is  increased,  is  not  opposed  to  the 
assumption  that  only  a  part  of  the  chemical  potential  energy 
is  transmitted  into  kinetic  energy  during  decomposition. 
The  two  processes,  decomposition  and  oxidation,  might  occur 
at  different  periods  ;  the  former  serves  for  muscular  work,  the 

1 L.  Hermann,  "  Unt.  üb.  d.  Stoffwechsel  der  Muskeln,  ausgehend  vom 
Gaswechsel  derselben"  :  Berlin,  1867. 


THE    SOURCE    OF    MUSCULAR    ENERGY  353 

latter  provides  heat.  Both  processes  might  also  be  separated 
as  to  their  locality,  the  decomposition  occurring  in  the  proto- 
plasm of  muscular  fiber,  while  possibly  the  oxidation  of  the 
decomposition  products  occurs  in  other  tissue-elements. 

From  this  point  of  view  the  absorption  of  oxygen  would 
mainly  serve  for  the  production  of  heat.  There  is  a  remarkable 
difference  in  animals  in  their  requirement  of  oxygen,  and 
it  appears  that  the  want  is  regulated  by  the  amount  of  heat 
generated.  A  mammal  requires  at  least  from  ten  to  twenty 
times  as  much  oxygen,  in  proportion  to  its  weight,  as  a  cold- 
blooded animal.  A  bird  uses  up  more  than  a  mammal,  A 
small  animal,  giving  off  more  heat  from  a  relatively  larger 
surface,  requires  more  than  closely  allied  animals  of  a  large 
size.  Young  animals  require  more  than  full-grown  animals  of 
the  same  species.  These  differences  are  well  shown  in  the 
following  table : 

Amount  of  Oxygen  Consumed  in  Twenty-Foue  Hours,  in  Pkoportion 
TO  1  Grm.  of  Weight,  in  c.cm.  at  0°  C.  and  760  mm.  Hg.i 

Sparrow 

Duck 

Dog 

Man 

Frog ...  

Earthworm 

Tench .        

Eel 

Lizard,  hibernating  . .    . 

If  it  is  correct  to  regard  muscular  energy  as  mainly  pro- 
duced by  the  decomposition  of  food,  and  heat  chiefly  by 
oxidation,  we  should  expect  that  animals  which  develop  no 
heat  would  require  the  smallest  amount  of  oxygen.  This  is 
the  case  with  the  entozoa  of  warm-blooded  animals,  which 
reside  in  a  uniformly  high  temperature.  We  know  that  the 
intestinal  parasites  live  in  a  medium  which  is  almost  entirely 
free  from  oxygen,  for  the  most  recent  and  most  careful 
analyses  of  intestinal  gases  have  demonstrated  no  oxygen  in 
them.  We  know  that  active  processes  of  reduction  occur  in 
the  intestinal  contents ;  that  they  constantly  give  rise  to 
nascent  hydrogen ;  that  sulphates  are  reduced  to  sulphids, 
and  oxid  to  suboxid  of  iron.  The  amount  of  oxygen  taken 
up  by  the  intestinal  parasites  must  therefore   be  excessively 

^  The  figures  given  for  the  consumption  of  oxygen  in  man  are  derived  from 
the  work  of  Pettenkofer  and  Voit  [Zeitschr.  f.  Biolog.,  vol.  ii.  pp.  486,  489  :  1866)  ; 
those  for  fish  from  that  of  Jolyet  and  Regnard  {Arch,  de  Physiol,  norm,  et  path., 
Serie  ii.  vol.  iv.  pp.  605,  608  :  1877).  The  remaining  figures  are  from  the  work 
of  Regnault  and  Reiset  {Ann.  de  Chim.  et  de  Phys.,  vol.  xxvi.:  1849). 

23 


161.0 

23.0  - 

-  32.0 

15.0  - 

-  23.0 

7.0  - 

-  11.0 

1.0  - 

-     2.0 

1.7 

1.3 

0.97- 

-     1.2 

0.41 

354  LECTUEE    XXIII 

small.  It  is  possible  that  they  attach  themselves  to  the  walls 
of  the  intestine  and  take  up  oxygen  which  is  diiFused  from 
the  tissues  of  the  bowel,  before  it  is  taken  possession  of  by 
the  reducing  substances  of  the  intestinal  contents.  But  it 
is  also  possible  that  mere  traces  of  oxygen  are  sufficient  for 
their  wants,  or  even  that  they  require  no  oxygen,  as  is  asserted 
of  certain  bacteria  and  fungi  (compare  above,  pp.  158,  244,  note 
3).  This  question  can  only  be  decided  experimentally.  I  have 
made  many  experiments  with  the  round  worm  (^Ascai-is  mystax) 
of  the  cat,  and  have  satisfied  myself  that  these  animals  can 
live  in  media  entirely  free  from  oxygen  for  from  four  to  five 
days,  and  be  extremely  active  during  the  whole  time.^  Who- 
ever has  seen  these  movements  must  be  convinced  that  oxidation 
is  not  the  source  of  muscular  energy  in  these  animals. 

The  objection  might  be  raised  that  they  have  a  store  of 
oxygen  in  their  bodies,  which  is  but  loosely  fixed.  We  must 
admit  this  possibility.  Ascarides  are  sometimes  found  in  the 
stomach.  It  is  possible  that  they  rise  into  the  upper  part  of 
the  digestive  tract  in  order  to  supply  themselves  with  oxygen. 
But  this  proceeding  has  no  analogy  with  what  is  observed  in 
higher  animals ;  as  soon  as  the  supply  of  oxygen  is  cut  off, 
the  store  contained  in  the  oxyhemoglobin  is  consumed  in  a  few 
minutes  and  the  animals  perish.  Pflüger  ^  and  Aubert  ^  have 
certainly  shown  that  frogs  may  remain  alive  for  several  days 
in  an  atmosphere  containing  no  oxygen,  but  only  at  a  very  low 
temperature,  which  causes  a  reduction  of  the  entire  metabolism 
of  these  animals  to  the  lowest  point.*  If  they  are  left  at  the 
temperature  of  the  room,  they  become  motionless  after  a  few 
hours  ;  while  ascarides  move  about  most  actively  at  a  tempera- 
ture of  38°  C.  for  several  days  in  media  devoid  of  all  oxygen. 
I  am  far  from  applying  to  higher  animals  the  conviction 
derived  from  the  observation  of  these  animals,  that  muscular 
energy  is  mainly  due  to  processes  of  decomposition.  Intestinal 
parasites,  which  are  constantly  surrounded  by  food-supplies, 
can  afford  to  be  wasteful  of  their  potential  energies,  and  only 
utilize  that  portion  of  them  which  is  converted  into  kinetic 
energy  by  mere  decomposition.     Such  a  proceeduig  would  be 

^  G.  Bunge,  Zeitschr.  f.  physiol.  Chem.,  vol.  viii.  p.  48  :  1883. 

2  Pflüger,  in  his  Arch.,  vol.  x.  p.  313  :  1875. 

3  Aubert,  ibid.,  vol.  xxiv.  p.  293  :  1881. 

*  As  we  might  cl  priori  expect,  we  find  that  in  cold-blooded  (Poikilothermie) 
animals,  a  rise  of  the  temperature  of  their  environment  causes  increased  metab- 
olism and  consumption  of  oxygen,  whereas  the  reverse  is  the  case  in  warm- 
blooded or  homoiothermic  animals.  A  critical  account  of  the  numerous  experi- 
ments by  which  this  statement  has  been  established  will  be  found  in  a  paper  by 
Voit,  Zeitschr.  f.  Biolog.,  vol.  iv.  p.  57:  1878.  Compare  also  Max  Eubner,  Du 
Bois'  Arch.,  pp.  38,  248 :  1885. 


THE   SOURCE   OF   MUSCULAR   ENERGY.  355 

purposeless  in  the  higher  animals.  I  have  already  mentioned 
the  reasons  in  favor  of  the  view  that  in  the  higher  animals 
oxygen  penetrates  through  the  capillary  walls  into  the  tissues 
(p.  244).  With  regard  especially  to  muscular  tissue,  we 
have  to  add  an  important  fact  to  the  reasons  adduced  :  the 
occurrence  of  hemoglobin  in  muscle.'  Both  probability  and 
analogy  justify  the  view  that  the  hemoglobin  performs  the 
same  functions  in  muscle  as  in  blood,  i.  e.,  that  of  oxygen- 
carrier. 

The  amount  of  kinetic  energy,  which  may  develop  by  mere 
decomposition  without  oxidation  from  the  chemical  potential 
energies  of  food,  is  much  too  small  adequately  to  explain  mus- 
cular work.  Let  us  first  consider  the  carbohydrates,  which 
certainly  are  the  chief  source  of  muscular  energy. 

Unfortunately  we  are  not  sufficiently  familiar  with  the 
nature  of  the  process  of  decomposition  of  the  carbohydrates 
in  muscle.  It  has  often  been  opined  that  they  break  up  in 
the  first  instance  into  sarcolactic  acid.^  Normal  blood  in- 
variably contains  some  lactic  acid ;  the  amount  increases  in 
tetanized  animals,  and  when  blood  is  artificially  passed  through 
a  living  and  working  muscle.^  But  it  appears  that  the  amount 
of  lactic  acid  formed  in  muscle  is  too  trifling  to  allow  this  proc- 
ess of  decomposition  to  serve  as  a  source  of  muscular  energy. 
At  any  rate,  we  do  not  know  how  much  of  the  carbohydrate 
in  muscle  undergoes  this  decomposition.  We  do  not  even 
know  whether  the  lactic  acid  occurring  in  muscle  is  formed 
from  the  carbohydrates.'*  It  is  possible  that  during  work 
there  is  not  more  lactic  acid  formed  in  the  muscle  than  during 
rest,  but  that  more  is  transmitted  to  the  blood.  Astaschewsky 
found  less  lactic  acid  in  the  tetanized  than  in  the  quiescent 
muscle.^     The  heat-equivalent  of  lactic  acid  has  never  been 


^  W.  Kühne,  Virchow's^r-cA.,  vol.  xxxiii.  p.  79  :  1865;  and  Ray  Lankester, 
Pflüger's  Arch.,  vol.  iv.  p.  315:  1871.  These  statements  with  regard  to  the 
occurrence  of  hemoglobin  in  muscle  have  been  repeatedly  doubted,  but,  as  it 
appears  to  me,  without  adequate  grounds.  Vide  St.  Zaleski,  Centralbl.  f.  d.  med. 
Wissensch.,  Nos.  5,  6  :  1887.    The  earlier  authors  are  here  mentioned. 

"■  Compare  above,  p.  312,  note  2. 

^  Vide  P.  Spiro,  Zeitschr.  f.  physiol.  Chem.,  vol.  i.  p.  Ill :  1877 ;  Max  von 
Frey,  Du  Bois'  Arch.,  p.  557  :  1885 ;  Gaglio,  ibid.,  p.  400  :  1886  ;  Wissokowitsch, 
ibid.,  Suppl.,  p.  91 :  1877 ;  and  M.  Berlinerblau,  Arch.  f.  exper.  Path.  u.  Pharm., 
vol.  xxiii.  p.  333  :  1887. 

*  In  favor  of  the  view  that  lactic  acid  arises  from  the  carbohydrate,  Ber- 
linerblau ( loc.  cit. )  points  out  that  when  blood  to  which  glucose  or  glycogen  has 
been  added,  is  artificially  passed  through  the  muscles,  more  lactic  acid  is  formed 
than  without  them.  Considerable  quantities  of  lactic  acid  are  formed  in  the 
dying  muscle,  but  whence  it  arises  is  entirely  unknown.  Roehm  has  shown  that 
it  is  not  formed  from  glycogen  (Pflüger's  Arch.,  vol.  xxiii.  p.  44  :  1880). 

^  Astaschewsky,  Zeitschr.  f. physiol.  Chem.,  vol.  iv.  p.  397  :  1880. 


356  LECTURE   XXIII 

determined,  so  that  we  are  unable  to  state  how  much  kinetic 
energy  is  liberated  during  lactic  fermentation. 

Let  us  endeavor  to  represent  to  ourselves  the  amount 
of  kinetic  energy  which  may  proceed  from  the  decomposition 
of  carbohydrates,  by  picturing  to  ourselves  two  processes  in 
which  the  amount  of  kinetic  energy  liberated  has  been  exactly 
determined :  alcoholic  fermentation  and  butyric  acid  fermenta- 
tion. The  amount  of  heat  liberated  during  the  latter  process 
is  larger  than  in  the  former,  and  we  may  assert  that  no  greater 
amount  of  heat  can  be  liberated  in  any  of  the  various  processes 
which  sugar  undergoes  in  decomposition.  For  of  the  three 
products  resulting  from  butyric  fermentation  (butyric  acid, 
carbonic  acid,  and  hydrogen),  only  butyric  acid  can  be  further 
broken  up,  and  but  little  heat  can  be  liberated  in  this  process. 
The  breaking  up  of  butyric  acid  into  propane  and  carbonic 
acid  is  entirely  analogous  to  the  splitting  up  of  acetic  acid 
into  methane  and  carbonic  acid  —  a  process  in  which  we  are 
equally  unable  to  show  a  development  of  heat.  Taking  the 
numbers  quoted  at  p.  62  as  a  foundation,  I  have  calculated  the 
combustion-heat  of  sugar  and  of  its  products  of  decomposition 
as  follows  : 

Calories,        Kgrms. 
or  metric      muscular 
heat-units.        work. 

1000  grms.  of  grape-sngar  on  complete  combustion 
to  CO2  and  HA  yield .  3939  =  1,674,000 

1000  grms.   of  grape-sugar,  when  split  up  into 

alcohol  and  CO2,  yield .      372=     158,100 

1000  grms.   of  grape-sugar,  when  split  up  into 

butyric  acid,  CO^,  and  H,  yield      ......      414  =     176,000 

The  amount  of  work  done  by  Wislicenus  in  as- 
cending the  Faulhorn  in  six  hours  amounted  to  148,656 

The  amount  of  work  done  by  heart  and  respira- 
tion during  the  same  ascent  amounted  to  ,    .    .  30,000 

Accordingly  we  see  that,  had  the  work  done  during  the 
ascent  of  the  Faulhorn  been  carried  out  by  the  decomposition 
of  carbohydrates,  more  than  1000  grms.  of  carbohydrates  would 
have  been  required  in  six  hours  !  This  is  out  of  the  question. 
On  the  other  hand,  100  grms.  of  sugar,  if  completely  broken 
up  and  oxidized,  would  have  sufficed  to  execute  the  work. 
This  amount  of  carbohydrate  is  always  stored  up  in  our  muscles, 
besides  an  equal  quantity  in  the  liver. 

I  think  that  my  calculation  proves  that  to  perform  their 
work  our  muscles  not  only  utilize  the  kinetic  energy  liberated 
by  the  decomposition  of  the  food,  but  that  oxygen  also  pene- 
trates the  protoplasm  of  muscular  fiber,  and  its  affinity  to  the 
products  of  decomposition  serves  as  a  source  of  energy. 


THE    SOURCE    OF    MUSCULAR    ENERGY  357 

Here  we  may  again  refer  to  the  question  of  the  value  of 
alcohol  as  a  food.  Even  if  we  grant  that  alcohol  is  turned 
to  account  in  the  body  as  a  source  of  energy,  yet  this  store 
of  energy  is  far  smaller  than  that  contained  in  the  carbohydrate 
from  which  the  alcohol  was  prepared.  In  the  fermentation 
of  a  kilogram  of  sugar,  as  we  have  just  seen,  an  amount  of 
energy  is  wasted  which  would  serve  to  carry  a  heavy  man 
to  the  top  of  the  Faulhorn.  We  must  remember  too  that 
certain  cells  of  our  body  can  probably  only  avail  themselves  of 
the  energy  set  free  in  the  breaking  down  of  food-stuflPs,  since  no 
free  oxygen  ever  reaches  them  (compare  p.  341).  We  thus 
see  how  foolish  it  is  for  men  to  give  the  nourishing  carbo- 
hydrates of  the  grape-juice  and  grain  to  be  devoured  by  the 
yeast-fungus,  while  they  themselves  feast  on  the  excreta  of  the 
fungus.  Fruit  berries,  and  milk  too,  are  deprived  of  all  their 
value  in  this  way. 


LECTURE   XXIV 


FORMATION    OF    FAT   IN   THE    ANIMAL    BODY 

The  question  regarding  the  origin  of  fat  in  the  tissues  of 
the  animal  body,  a  most  important  part  of  metabolism,  remains 
for  our  consideration.  Our  views  on  this  subject  have  under- 
gone constant  fluctuations  and  controversies  during  the  last 
few  decades ;  but  we  have  arrived  at  the  conviction,  after 
many  and  careful  experiments,  that  the  fat  in  the  tissues 
may  be  formed  from  all  the  three  chief  classes  of  organic 
food-stuffs,  viz.,  from  the  fats,  the  proteids,  and  the  carbo- 
hydrates. 

From  the  comprehensive  literature  on  the  formation  of  fat,^ 
I  shall  select  those  works  which  constitute  the  firmest  basis  of 
our  present  knowledge  of  this  subject. 

It  was  long  doubted  whether  the  fat  of  the  tissues  was 
derived  from  the  fat  of  the  food  ;  chiefly  on  the  grounds  that 
fat,  being  absolutely  insoluble  in  water,  could  not  as  such 
penetrate  the  intestinal  wall,  and  that  it  would  previously 
have  to  be  converted  in  the  bowel  into  a  soluble  soap  and 
soluble  glycerin.  The  view  that  glycerin  and  fatty  acids 
might  again  unite  in  the  tissues  on  the  other  side  of  the 
intestinal  wall  was  opposed  by  the  belief  that  no  syntheses 
could  occur  in  the  animal  body.  We  have  seen  that  both 
these  objections  have  now  been  overcome ;  we  know  that 
all  kinds  of  synthetic  processes  occur  in  the  animal  body, 
and  that  neutral  fat  does  pass  through  the  intestinal  wall. 
Now,  if  fat  globules  permeate  the  tissues  of  the  intestine, 
why  may  they  not  pass  through  the  walls  of  the  capillaries 
and  through  all  the  organs  of  our  body  ?  Ä  priori  therefore, 
there  is  nothing  opposed  to  the  view  that  the  fat  of  our  tissues 
is  derived  from  the  fat  of  our  food.  Franz  Hofmann^  was  the 
first  to  give  experimental  proof  that  this  is  the  case. 

1  Voit  supplies  an  interesting  survey  of  the  older  literature  on  this  subject. 
"  Ueber  die  Fettbildung  im  Thierkörper,"  Zeitschr.  f.  Biolog.,  vol.  v.  p.  79 :  1869. 
Compare  also  "Ueber  die  Entwiekelung  der  Lehre  von  der  Quelle  der  Muskel- 
kraft und  einiger  Theile  der  Ernährung  seit  25  Jahren,"  ibid.,  vol.  vi.  p.  371 : 
1870. 

*  Franz  Hofmann,  Zeitschr.  f.  Biolog.,  vol.  viii.  p.  153:  1872. 

358 


FOEMATION   OF   FAT   IN   THE   ANIMAL   BODY  359 

Hofmann  deprived  a  dog  of  all  fat  by  starving  him  for 
thirty  days.  We  are  able  to  determine  the  exact  period  when 
all  the  fat  that  is  stored  in  the  tissues  is  consumed.  We 
have  already  seen  that  a  starving  animal  at  first  lives  mainly 
upon  its  store  of  glycogen,  and  subsequently  upon  its  fat. 
It  uses  the  greatest  economy  with  regard  to  its  proteid. 
That  very  little  of  the  latter  is  decomposed  is  shown  by  the 
minute  excretion  of  nitrogen,  which  at  first  falls,  and  then 
remains  almost  permanently  the  same.  It  is  only  after  a 
longer  period,  which  may  vary  from  the  fourth  to  the  fifth 
we'ek  according  to  the  original  amount  of  fat,  that  a  sudden 
rapid  increase  takes  place  in  the  excretion  of  nitrogen.  This 
is  the  period  at  which  the  store  of  fat  is  used  up,  and  when  the 
animal  commences  to  depend  exclusively  upon  its  store  of 
proteid.  The  animal  will  now  speedily  perish.  If  the  animal  is 
killed  at  the  time  when  the  sudden  increase  of  the  nitrogenous 
excretion  occurs,  all  the  organs  and  tissues  are  found  to  be 
deprived  of  fat.  If  it  is  killed  earlier  a  certain  amount  of  fat 
is  still  found.^ 

Armed  with  this  knowledge,  Hofmann  was  able  to  determine 
when  his  starving  dog  was  free  from  all  fat.  He  now  fed  him 
on  a  diet  containing  a  great  deal  of  fat  and  but  little  proteid, 
viz.,  bacon  and  a  small  quantity  of  meat.  The  amount  of 
proteid  and  fat  in  the  food  had  been  accurately  estimated. 
After  five  days  the  animal  was  killed,  and  the  amount  of  fat 
and  proteid  remaining  in  the  intestine,  as  well  as  the  fat  in 
the  whole  body,  was  measured.  It  was  found  that  during  the 
five  days  the  dog  had  absorbed  1854  grms.  of  fat  and  254  grms. 
of  proteid,  and  had  deposited  1353  grms.  of  fat  in  his  body. 
This  large  amount  of  fat  could  not  have  arisen  from  the  proteid. 
It  follows  therefore  that  the  fat  of  the  food  had  been  deposited 
in  the  tissues. 

Pettenkofer  and  Voit  ^  obtained  the  same  result  by  a  dif- 
ferent method.  They  fed  dogs  with  fat  and  a  little  meat, 
and  by  the  use  of  the  respiratory  apparatus  they  measured 
the  total  income  and  output.  Their  experiments  showed  that 
all  the  nitrogen  consumed  was  reexcreted,  but  not  all  the 
carbon.  A  very  large  proportion  of  the  carbon  was  retained. 
It  was  to  be  inferred  that  a  non-nitrogenous  compound  had 
been  stored  in  the  tissues,  and  this  could  be  nothing  but  fat, 
because  there  is  no   other    non-nitrogenous    compound    which 

^  When  the  fasting  animal,  at  the  commencement  of  the  experiment,  is  un- 
usually fat,  it  may  happen  that  it  dies  from  failure  of  its  proteids  even  before  the 
supply  of  fat  is  consumed. 

2  Pettenkofer  and  Voit,  Zeitschr.  f.  Biolog.,  vol.  ix.  p.  1 :  1873. 


360  LECTUEE  xxrv 

is  met  with  in  the  tissues  in  such  large  quantities.  The  fat 
deposited  in  the  tissues  could  not  be  due  to  the  decomposed 
proteid,  as  its  amount  was  proportionately  too  large.  It  was 
possible  to  calculate  with  precision  how  much  proteid  had 
been  decomposed  by  the  quantity  of  nitrogen  excreted.  The 
maximum  amount  of  fat  formed  from  the  decomposed  proteid 
could  be  calculated  on  the  assumption  that  the  nitrogen  had 
been  separated  from  the  proteid  molecule  as  urea.  The  amount 
of  fat  resulting  from  this  calculation  was  much  less  than  that 
actually  found  in  the  body  ;  it  was  therefore  evident  that  this 
must  be  derived  from  the  fat  of  the  food. 

We  must  now  inquire  whether  it  is  only  that  portion  of 
the  fat  of  food  which  is  absorbed  unaltered  as  a  neutral 
glycerid  that  can  be  stored  up  in  the  tissues,  or  whether  that 
part  which  is  split  up  in  the  intestine  (compare  pp.  164—166) 
can  also  be  regenerated  and  assimilated. 

Munk  ^  has  recently  performed  the  most  careful  investi- 
gations to  determine  this  question.  He  showed,  in  the  first 
instance,  that  free  fatty  acids  are  absorbed  from  the  intestine 
in  large  quantities  as  neutral  fats.  If  free  fatty  acids  are 
shaken  up  with  a  dilute  solution  of  alkaline  salts,  a  small 
portion  of  the  fatty  acids  is  saponified,  the  remainder  is  emul- 
sified ;  the  same  takes  place  in  the  intestine.  Dogs,  after  the 
consumption  of  a  large  quantity  of  free  fatty  acids,  exhibited 
only  a  very  small  portion  in  their  feces,  but  their  chyle-ducts 
were  full  of  a  white  emulsion. 

The  same  inquirer  also  proved  that  free  fatty  acids  exercise 
the  same  economizing  effect  upon  proteids  as  neutral  fats. 
A  carnivorous  animal,  in  order  to  maintain  its  body  weight, 
requires  nearly  one-twentieth  of  this  weight  daily  of  lean 
meat.^  A  dog  weighing  25  kgrms.  consequently  requires 
1200  grms.  of  meat.  If  we  give  him  less,  he  excretes  more 
nitrogen  than  he  consumes,  and  he  feeds  upon  the  proteids 
of  his  tissues.  But  if  we  add  fat  to  the  meat  of  his  food, 
the  dog,  although  consuming  less  meat,  maintains  his  nitro- 
genous equilibrium.^  Munk  established  the  nitrogenous 
equilibrium  in  a  dog  weighing  25  kgrms.  with  800  grms.  of 
meat  and  70  grms.  of  fat,  and  then  showed  that  this  equi- 
librium remained  the  same  if,  instead  of  the  70  grms.  of  fat, 

1  Immanuel  Munk,  Du  Bois'  Arch.  f.  Physiol.,  p.  371  :  1879;  and  p.  273: 
1883  ;  Yirchow's  Arch.,  vol.  Ixxx.  p.  10 :  1880  ;  and  vol.  xcv.  p.  407 :  1884.  The 
earlier  literature  is  here  quoted. 

*  Bidder  and  Schmidt,  "  Die  Verdauungssäfte  und  der  Stoffwechsel,"  p.  333  : 
Mitau  and  Leipzig,  1852;  Pettenkofer  and  Voit,  Ann.  d.  Chem.  u.  Pharm., 
SuppL.ii.  p.  361:  1862. 

*  Munk,  Virchow's  Arch.,  vol.  Ixxx.  p.  17  :  1880. 


FORMATION    OF    FAT   IN   THE   ANIMAL,   BODY  361 

lie  gave  the  dog,  with  the  same  amount  of  meat,  the  free 
fatty  acids  obtained  from  the  70  grms.  of  fat.  In  a  second 
experiment,  the  nitrogenous  equilibrium  was  produced  in  a 
dog  weighing  31  kgrms.  with  600  grms.  of  meat  and  100 
grms.  of  fat,  and  this  was  maintained  when  subsequently  the 
free  fatty  acids  of  100  grms.  of  fat  were  given  him  with  the 
same  amount  of  meat  for  three  weeks. 

The  important  fact  has  further  been  determined  by  Munk^ 
that,  after  feeding  with  free  fatty  acids,  only  a  very  small 
quantity  of  fatty  acids  and  soaps,  but  much  neutral  fat,  was 
contained  in  the  chyle.  He  fed  dogs  with  meat  and  fatty 
acids,  and  introduced  a  cannula  into  the  thoracic  duct ;  a  few 
hours  later,  he  determined  the  amount  of  chyle  flowing  out, 
and  the  quantity  of  neutral  fat,  fatty  acids,  and  saponified 
matter  contained  in  it.  He  found  that,  in  the  same  time, 
from  ten  to  twenty  times  more  neutral  fat  passes  through  the 
thoracic  duct  than  during  the  digestion  of  pure  proteids,  while 
the  amount  of  soaps  remains  unaltered.  The  proportion  of  the 
free  fatty  acids  generally  reached  only  to  between  one-twentieth 
and  one-tenth,  in  one  case  less  than  one-thirtieth,  of  the  neutral 
fats.  It  follows  that  a  synthesis  of  fatty  acids  with  glycerin 
takes  place  during  the  passage  from  the  intestinal  surface  to 
the  thoracic  duct.^  We  have  no  precise  information  as  to  the 
locality  where  this  synthesis  is  effected.  It  may  be  in  the 
epithelial  cells,  in  the  adenoid  tissue  of  the  intestine,  or  in 
the  lymphatic  glands  of  the  mesentery.  A  preliminary  com- 
munication made  by  Ewald  ^  shows  that  this  synthesis  also 
occurs  in  the  intestinal  mucous  membrane  after  it  has  been 
excised. 

We  do  not  know  the  source  from  which  the  glycerin  arises 
that  is  necessary  for  this  synthetic  process.  At  all  events, 
Munk's  experiment  proves  that  the  glycerin  in  the  fat  of  our 
body  need  not  always  be  derived  from  the  fat  of  our  food ;  it 
may  possibly  result  from  the  breaking  up  of  the  proteids  and 
carbohydrates. 

We  must  confess  that  the  fate  of  the  glycerin  in  our  body 
is  entirely  unknown  to  us,  and  at  present  we  are  unable  to 
say  what  becomes  of  the  glycerin  which  is  separated  in  the 

^  Munk,  Virchow's  Arch.,  vol.  Ixxx.  p.  28,  et  seq.:  1880. 

^O.  Minkowski  (Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxi.  p.  373:  1886) 
arrived  at  the  same  result.  He  had  the  opportunity  of  experimenting  on  a 
patient  suffering  from  extreme  ascites,  the  result  of  a  rupture  of  a  chyle-vessel. 
A  large  quantity  of  chyle  was  obtained  by  puncture.  After  administering  to  this 
patient  free  erucic  acid,  the  neutral  glycerid  of  this  acid  was  detected  in  the 
chyle. 

3  C.  A.  Ewald,  Du  Bois'  Arch.,  p.  302:  1883. 


362  LECTURE    XXIV 

intestine  from  the  fat.  If  a  large  quantity  of  glycerin  is 
introduced  into  the  stomach  of  a  man  or  a  dog,  diarrhea  occurs, 
and  of  the  glycerin  that  is  absorbed  a  portion  passes  unaltered 
into  the  urine/  Smaller  quantities  do  not  produce  such  con- 
sequences ;  in  the  dog,  the  proportion  ought  not  to  exceed 
1.5  grm.  to  1  kgrm.  of  weight. 

Finally,  Munk  has  given  definite  proof  that  the  fat 
synthetically  formed  is  also  stx)red  up  in  the  tissues  of  the 
body.'  A  dog  weighing  16  kgrms.  was  rendered  almost 
devoid  of  fat  by  starvation  for  nineteen  days,  during  which 
time  he  lost  32  per  cent,  of  his  original  weight.  In  the 
course  of  the  next  fourteen  days  the  dog  consumed  3200 
grms.  of  meat,  and  2850  grms.  of  fatty  acids  prepared  from 
mutton  fat.  With  this  diet,  its  weight  rose  again  by  17  per 
cent.  The  animal  was  now  killed,  and  showed  an  enormously 
developed  panniculus  adiposus;  there  was  a  copious  deposit 
of  fat  in  the  intestines,  and  a  well-marked  fatty  liver.  The 
deposit  of  fat  removed  by  scalpel  and  scissors  yielded  nearly 
1100  grms.  of  fat  that  was  solid  at  the  temperature  of  the 
room,  and  only  melted  at  a  temperature  of  40°  C.  while  normal 
dog's  fat  is  semi-fluid  at  20°.  It  follows  that  the  fatty  acids 
which  had  been  introduced  were  deposited  after  combining 
with  glycerin  that  had  formed  in  the  body.  If  the  deposit 
of  fat  be  attributed  to  an  economizing  influence,  exercised 
by  the  fatty  acids  introduced,  and  all  the  fat  deposit  be 
regarded  as  entirely  originating  from  the  proteid,  it  is  not 
intelligible  why  mutton  fat  was  deposited  instead  of  normal 
dog's  fat. 

In  a  second  experiment,^  Munk  fed  a  dog,  which  had  been 
deprived  of  fat  by  starvation,  with  colza  oil.  In  this  case 
four-fifths  of  the  fat  deposited  in  the  organs  were  liquid  at 
the  temperature  of  the  room ;  when  warmed  to  23°,  the  whole 
of  it  melted  ;  and  at  14°  a  granular  crystalline  sediment  formed. 
This  fat  contained  82.4  per  cent,  of  oleic  acid,  and  12.5  per 
cent,  of  fixed  acids ;  whereas  normal  dog's  fat  yields  on  an 
average  only  65.8  per  cent,  of  oleic  and  28.8  per  cent,  of  solid 
acids.  In  addition  to  this,  erucic  acid  (CjgH^^Og);  which  is  an 
ingredient  of  colza  oil  but  absent  from  animal  fat,  was  proved 
to  be  present. 

Previous   to    Munk,    two    similar    experiments   had   been 

'  B.  Luchsinger,  "Experimentelle  und  kritische  Beiträge  zur  Physiologie 
und  Pathologie  des  Glycogens."  Inaug.  Dissert.,  p.  38,  et  seq.:  Zurich,  1875 ; 
Munk,  Virchow's  Arch.,  vol.  Ixxx.  p.  39,  et  seq. :  1880;  Arnschink,  Zeitschr.  f. 
Biolog.,  vol.  xxiii.  p.  413  :  1887. 

2  J.  Munk,  Du  Bois'  Arch.,  p.  273  :  1883. 

*  J.  Munk,  Virchow's  Arch.,  vol.  xcv.  p.  407  :  1884. 


FORMATION    OF    FAT    IN    THE    ANIMAL    BODY  363 

carried  out  by  Lebedeff'  with  the  same  result  in  two  dogs, 
one  of  which  had  been  fed  with  linseed  oil,  the  other  with 
mutton  fat.  The  fat  in  the  tissues  of  the  former  did  not 
congeal  at  0°,  the  fat  of  the  latter  had  a  melting-point  at 
above  50°. 

All  these  experiments  prove  conclusively  that  the  fat  of 
food  is  absorbed  and  deposited  unchanged. 

We  will  now  consider  the  second  point  as  to  whether  fat 
is  formed  from  Proteid  in  the  animal  body.  As  fat  takes 
the  place  of  proteid  in  the  cells  and  fibers  in  cases  of  fatty 
degeneration,  we  should  suppose  that  fat  necessarily  proceeds 
from  this  source.  But  this  fact  cannot  be  interpreted  as 
absolute  proof  of  the  origin  of  fat  from  proteid.  We  must 
not  forget  that  in  the  living  body  there  is  a  constant  nutritive 
interchange  going  on  directly  or  indirectly  between  all  the 
tissue-elements.  It  is  possible  that  in  cases  of  fatty  degene- 
ration the  proteids  or  their  decomposition-products  may  pass 
away  from  the  degenerating  tissues,  and  be  replaced  by  fat  or 
its  components  from  other  tissues. 

An  exact  quantitative  examination  of  the  total  metabolism 
during  a  process  of  fatty  degeneration,  such  as  occurs  in 
phosphorus-poisoning  in  which  all  parts  of  the  body  are 
rapidly  involved,  would  show  whether  fat  arose  from  proteid 
or  not.  The  most  careful  investigation  of  this  process  was 
carried  out  in  Voit's  laboratory  at  Munich  by  J.  Bauer.^  He 
estimated  the  output  of  nitrogen  and  carbonic  acid  and  the 
income  of  oxygen  in  fasting  dogs.  He  then  poisoned  them 
with  phosphorus,  which  was  either  given  them  by  mouth  in 
small  doses  spread  over  several  days,  or  subcutaneously  in- 
jected dissolved  in  oil.  The  consequence  was  that  double  the 
amount  of  nitrogen  was  eliminated,^  and  that  the  -amount  of 
carbonic  acid  excreted  and  of  oxygen  absorbed,  dropped  to 
one-half.  The  nitrogen  from  a  large  amount  of  proteid  there- 
fore was  split  off  with  a  small  quantity  of  carbon  by  the  action 
of  the  phosphorus ;  a  remnant  free  from  nitrogen  remained 
unconsumed  in  the  body.  If  the  animals  died  a  few  days  after 
the  administration   of  phosphorus,  a   post-mortem  examination 


'  A.  Lebedeff  (Salkowski's  laboratory  in  Berlin),  3Ied.  Centralbl.,  No.  8  : 
1882. 

2  Jos.  Bauer,  Zeitschr.  f.  Biolog.,  vol.  vii.  p.  63  :  1871 ;  and  vol.  xiv.  p.  527  : 
1878. 

'  The  increase  in  the  excretion  of  nitrogen  after  phosphorus-poisoning  was 
shown  before  Bauer  by  O.  Storch,  "Den  acute  Phosphorforgiftning,"  &c., 
Dissert. :  Kjobenhavn,  1865.  Paul  Cazeneuve  has  confirmed  Storch's  and 
Bauer's  results  in  the  Revue  mensuelle  de  Medec.  et  de  Chirurg.,  vol.  iv.  pp.  265, 
444:  1880. 


364  LECTURE    XXIV 

showed  all  the  organs  to  be  in  a  state  of  fatty  degeneration. 
In  one  case,  the  dried  muscles  contained  42.4  per  cent.,  the 
dried  liver  30  per  cent,  of  fat,  whereas  only  16.7  per  cent,  was 
found  in  normal  dried  dog's  muscle  and  only  10.4  per  cent,  in 
normal  dried  liver.  Fat  was  therefore  formed  from  proteid  in 
phosphorus-poisoning.  It  cannot  be  objected  that  the  fat  had 
passed  in  from  the  fatty  connective  tissue  in  the  muscles  and 
in  the  liver,  because  the  dog  had  been  starved  for  twelve 
days  before  the  commencement  of  the  poisoning,  and  died  on 
the  twentieth  day  of  starvation.  But  experience  has  shown 
that  in  dogs  all  fat  visible  to  the  naked  eye  disappears  from 
the  subcutaneous  cellular  tissue  and  the  mesentery  after  twelve 
days  of  starvation. 

Arsenic  and  antimony,  which  are  chemically  so  closely 
related  to  phosphorus,  seem  to  operate  in  a  similar  manner. 
They  need  not  however  be  administered  as  free  elements,  as 
they  also,  when  in  the  oxidized  condition,  cause  increased 
elimination  of  nitrogen  and  fatty  degeneration  of  the  organs.^ 
We  are  at  present  unable  even  to  suggest  an  explanation  of 
this  action. 

The  experiments  with  phosphorus-poisoning  only  prove  the 
origin  of  fat  from  proteid  under  these  definite  abnormal  con- 
ditions. The  question  is  whether  this  conversion  likewise  takes 
place  under  normal  circumstances. 

The  following  simple  experiment  made  by  Franz  Hofmann^ 
on  fly-maggots,  undoubtedly  proves  that  fat  does  arise  from 
proteid  under  normal  conditions.  It  is  an  easy  matter  to 
collect,  free  from  impurity,  the  eggs  of  the  Museida  vomitoria, 
which  are  laid  in  heaps  on  a  corpse  in  the  summer-time. 
Part  of  the  eggs  so  obtained  was  employed  by  Hofmann  to 
estimate  the  amount  of  fat ;  the  other  part  was  allowed  to 
develop  on  blood.  The  fat  in  the  blood  was  also  determined. 
After  the  maggots  were  full-grown,  the  fat  in  them  was  like- 
wise ascertained.  It  was  found  that  there  was  ten  times  as 
much  fat  in  the  full-grown  maggots  as  in  the  eggs  and  blood 
together.  For  instance,  in  one  experiment,  0.02  grm.  of  eggs 
containing  0.001  grm.  of  fat  developed  in  52  grms.  of  blood, 
which  had  0.017  grm.  of  fat,  the  full-grown  maggots  contain- 
ing 0.201  grm.  of  fat.  This  can  only  have  been  formed  from 
the  proteid  of  the  blood  ;  it  cannot  be  referred  to  the  sugar  of 

^Gähtgens,  Centralbl.  f.  d.  med.  Wissensch.,  -p.  529:  1875;  Kossel,  Arch.f. 
exper.  Path.  u.  Pharm.,  vol.  v.  p.  128 :  1876 ;  Gähtgens,  ibid.,  vol.  v.  p.  833 : 
1876;  and  Centralbl.  /.  d.  med.  Wissench.,  p.  321:  1876;  and  Salkowsky, 
Virchow's  Arch.,  vol.  xxxiv.  p.  73:  1865. 

2  Franz  Hofmann,  Zeitschr.f.  Biolog.,  vol.  viii.  p.  159  :  1872. 


FORMATION    OF    FAT    IN    THE    ANIMAL    BODY  365 

the  blood,  for  50  grms.  of  blood  seldom  contains  more  than 
0.07  grm.  of  sugar,  and  even  this  far  too  small  a  quantity  must 
have  decomposed  very  rapidly;  besides,  the  maggots  had  not 
consumed  nearly  all  the  blood. 

From  the  following  experiments  on  dogs,  Pettenkofer  and 
Voit^  came  to  the  conclusion  that  fat  may  be  formed  from 
proteid  in  mammals  with  a  normal  dietary.  They  fed  them 
on  large  quantities  of  lean  meat,  and  with  the  help  of  the  respi- 
ratory apparatus  they  determined  the  total  income  and  output. 
It  was  found  that  all  the  nitrogen,  but  not  all  the  carbon,  of 
the  meat  reappeared  in  the  excretions.  In  one  experiment,^ 
for  instance,  in  which  a  dog  of  34  kgrms.  weight  ate  2800 
grms.  of  meat,  the  whole  of  the  nitrogen  was  eliminated, 
against  only  271  grms.  of  the  carbon,  of  which  313  grms. 
had  been  taken ;  42  grms.  were  therefore  missing.  These 
remained  behind  in  the  body  as  a  non-nitrogenous  compound, 
and  moreover,  as  Pettenkofer  and  Voit  concluded,  in  the  form 
of  fat.  It  may  be  objected  that  this  compound  may  have 
been  glycogen  just  as  well  as  fat.  The  amount  of  glycogen 
stored  in  the  body  of  the  Carnivora  is  by  no  means  inconsider- 
able, and  varies  widely.  Böhm  and  Hofmann^  found  it 
amounted  from  1.5  to  8.5  grms.  per  kilogramme  of  a  cat's 
weight.  The  42  grms.  of  carbon  correspond  to  about  100 
grms.  of  carbohydrates.  If  therefore  we  assume  that  the 
former  are  stored  in  this  form,  there  must  be  an  increase  of 
glycogen  amounting  to  3  grms.  per  kilogramme  of  the  body- 
weight,  which  does  not  appear  impossible.  But  we  ought 
not  to  forget  that  this  increase  of  glycogen  must  take  place 
in  one  day ;  the  animal  had  had  the  same  food  on  the  previous 
day,  therefore  so  great  a  change  in  the  amount  of  glycogen 
was  not  very  probable.  But  the  experiments  must  be  con- 
tinued over  a  longer  time  before  this  point  can  be  definitely 
settled.  It  might  however  be  decided  in  another  way,  i.  e., 
if  it  were  possible  to  make  an  exact  comparison  of  the  income 
and  output  of  oxygen.  The  difference  in  the  amount  of 
oxygen  in  fat  and  glycogen  is  very  considerable.  It  must 
therefore  be  possible  to  determine  the  form  in  which  carbon 
is  stored  up  from  the  quantity  of  the  oxygen  remaining  in 
the  body.  But  at  present  we  have  no  method  of  directly 
estimating  the  amount  of  oxygen  in  food,  and  even  the  in- 

^  Pettenkofer  and  Voit,  Liebig's  Annal.,  Suppl.  ii.  p.  361 :  1862;  Zeitschr. 
/.  Biolog.,  vol.  vi.  p.  377  :  1870 ;  and  vol.  vii.  p.  433  :  1871. 

2  Ibid.,  vol.  vii.  p.  487 :  1871. 

'  Böhm  and  Hofmann,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  viii.  p.  290: 
1878. 


366  LECTURE   XXIV 

spired  oxygen  is  calculated,  according  to  Pettenkofer's  method, 
from  the  diiFerence. 

One  more  objection  may  be  raised  to  the  experiment  made 
by  Pettenkofer  and  Voit,  i.  e.,  that  the  meat  was  not  quite  free 
from  fat  and  carbohydrates.  The  formation  of  fat  from 
proteid  in  the  organism  of  the  mammal  under  normal  con- 
ditions has  therefore  not  yet  been  decisively  proved.^  But  it 
is  however  highly  probable,  because  it  is  certainly  the  case 
with  the  lower  animals  under  normal  circumstances,  and 
with  mammals  under  pathological  conditions.  Moreover,  it 
may  be  adduced  in  favor  of  the  normal  formation  of  fat 
from  proteid  that,  as  we  have  already  seen  (p.  345),  gly- 
cogen owes  its  origin  to  proteid,  and  fat  to  glycogen,  and  in 
fact  to  any  carbohydrates,  as  will  be  shown  directly.  No 
chemical  explanation  of  the  formation  of  fat  from  proteid  can 
at  present  be  oifered.  However,  the  process  must  not  be  re- 
garded as  of  so  simple  a  nature  that  the  fat  is  immediately  split 
off  from  the  gigantic  proteid-molecule  as  a  preformed  radical. 
Profound  decompositions,  metamorphoses,  and  consequent  syn- 
theses are  going  on,  of  which  we  cannot  at  present  form  even 
a  conception. 

We  now  come  to  the  third  and  last  point,  as  to  whether 
the  CARBOHYDRATES  are  converted  into  fat  in  the  animal  body. 
From  the  numerous  experiments  made  on  this  subject,  we 
will  select  the  following,  as  being  perfectly  reliable  in  their 
results. 

N.  Tschervinsky  ^  made  his  experiments  with  young  pigs. 
In  one  he  used  two  of  ten  weeks  old  from  the  same  litter, 
No.  1  weighing  7300  grms.,  and  No.  2  7290  grms.  It  would 
therefore  be  supposed  that  each  had  about  the  same  proportion 
of  fat  and  proteid  as  the  other.  No.  1  was  killed,  and  all  the 
fat  in  the  body  was  estimated,  as  well  as  the  nitrogen,  from 
which  the  maximum  of  proteid  was  determined.  No.  2  was 
then  fed  on  barley  for  four  months.  The  barley  was  analyzed, 
and  an  account  was  kept  of  the  barley  consumed.  The 
amount  of  undigested  fat  and  proteid  was  also  estimated  by 
analysis  of  the  excretions ;  and  in  this  way,  the  quantity  of 

1  The  remaining  experiments  quoted  in  favor  of  the  view  that  fat  is  formed 
from  proteid  are  likewise  inconclusive.  Compare  Subbotin,  Virchow's  Arch., 
vol.  xxxvi.  p.  561 :  1866 ;  and  Kemmerich,  Centralbl.  f.  d.  med.  Wissensch.,  p.  465  : 
1866 ;  and  p.  127  :  1867.  Compare  also  Pfliiger's  criticism  of  Voit's  experiments, 
Pflüger's  Arch.,  vol.  li.  pp.  229  and  317  :   1891. 

2  N.  Tschervinsky,  ZancZw.  Versuchsstationen,  vo\.  xxix.  p.  317  :  1883.  Ex- 
periments of  a  similar  character  by  other  authors  led  to  the  same  results  (F. 
Soxhlet,  Zeitschr.  d.  landwirthschaftlichen  Vereins  in  Bayern,  August-Heft,  1881 ; 
B.  Schulze,  Landw.  Jahrb.,  1,  57 :  1882 ;  St.  Chaniewski,  Zeitschr.  f.  Biolog., 
vol.  XX.  p.  179:  1884). 


FOEMATION   OF   FAT   IN   THE   ANIMAL,   BODY  367 

these  two  substances  absorbed  by  the  animal  in  the  four 
mouths  was  ascertained.  The  animal,  whose  weight  had  in- 
creased to  24  kgrms.,  was  now  killed,  and  the  proportion  of 
proteid  and  fat  in  the  whole  body  determined. 

No.  2  contained  .    .    .    .  2.52  kgrms.  proteid,  and  9.25  kgrms.  fat. 
No.  1         "  ....  0.96      "  "  "   069      "         " 

Thus  there  were  added  .  156      "  "  "   8.56      "         " 

Taken  up  with  the  food  .  7.49      "  "  "0^     " 

Difference  ...  —5.93  +7.9 

Thus  7.9  kgrms.  of  fat  had  been  added  in  the  body  —  an 
amount  which  could  not  have  originated  from  the  fat  of  the 
food ;  of  this  only  the  smallest  portion  could  have  arisen 
from  the  5.93  of  the  proteid  that  was  derived  from  the  food, 
and   was   not   deposited   in   the   form   of    proteid.     At   least 

5  kgrms.  of  fat  must  therefore  owe  its  origin  to  the  carbo- 
hydrates of  the  diet.  This  is  so  large  a  proportion  as  to 
refute  all  doubts,  and  particularly  the  objection  that  the 
identity  in  the  amount  of  fat  and  proteid  in  both  animals, 
upon  which  the  whole  experiment  rests,  as  an  arbitrary 
assumption. 

A  different  method  was  adopted  by  Meissl  and  Strohmer.^ 
They  fed  a  one-year-old  Yorkshire  pig  (a  good  fattening 
breed),  weighing  140  kgrms.,  for  seven  days  upon  rice,  which 
is  poor  in  fat  and  proteids  and  rich  in  carbohydrates.  Two 
kgrms.  were  administered  to  the  animal  every  day.  The 
rice  had  been  analyzed ;  the  urine  and  feces  were  collected 
and  also  analyzed.  On  the  third  and  sixth  days  of  the 
experiment  the  animal  was  placed  in  Pettenkofer's  respira- 
tory apparatus,  in  order  to  determine  the  excretion  of  carbonic 
acid.  The  result  was  that  289  grms.  of  the  carbon  daily  in- 
gested, and  6  grms.  of  the  nitrogen,  were  retained  in  the  body  : 
38  grms.  of  proteid  with  20  grms.  of  carbon  correspond  to  the 

6  grms.  of  nitrogen.  It  follows  that  269  grms.  of  carbon  must 
have  been  daily  retained  in  the  body  as  fat.  It  is  impossible 
that  so  large  a  quantity  of  carbon  could  every  day  have  been 
stored  up  as  glycogen.  How  then  was  this  quantity  of  fat 
formed?  Of  the  daily  food,  5.3  grms.  of  fat  and  104  grms. 
of  proteid  had  been  digested ;  of  the  latter,  38  grms.  had  been 
deposited.  The  remaining  66  grms.  of  proteid  and  the  5.3 
grms.  of  fat  cannot  have  yielded  the  269   grms.  of  carbon 


^E.  Meissl  and  F.  Strohmer,  Sitzungsher.  d,  k.  Akad.  d.  Wissensch.  iyiWien., 
vol.  Ixxxviii.,  Abth.  III.,  Juli-Heft,  1883. 


368  LECTURE    XXIV 

necessary  for  the  deposit  of  fat,  which  must  therefore  be  derived 
from  the  carbohydrates. 

It  has  often  been  asserted  that  the  formation  of  fat  from 
carbohydrates  takes  place  only  in  herbivora  and  omnivora, 
and  not  in  Carnivora.  I  therefore  briefly  mention  the  following 
experiment,  which  Rubner/  with  the  help  of  a  respiratory 
apparatus,  made  on  a  dog.  The  animal,  after  fasting  two 
days,  was  fed  on  cane-sugar  and  starch.  A  large  quantity  of 
carbon  was  retained  —  much  too  large,  in  fact,  to  be  accounted 
for  by  the  deposit  of  glycogen ;  it  follows  that  fat  had  been 
formed  from  carbohydrates. 

The  formation  of  fät  from  carbohydrates  offers  a  complete 
enigma  to  the  chemist,  and,  more  than  anything  else,  proves 
that  the  synthetic  processes  occurring  in  the  animal  cell  are 
as  complicated  as  those  in  the  vegetable  cell. 

Many  attempts  have  been  made  to  utilize  our  knowledge 
with  regard  to  the  formation  of  fat,  in  order  to  determine  the 
causes  of  corpulency  in  man,  and  the  means  of  counteracting 
and  preventing  it.  The  error  has  been  committed  of  attribut- 
ing the  cause  of  obesity  to  too  ample  a  diet,  or  even  to  an 
unsuitable  combination  of  food,  such  as  a  diet  with  an  excessive 
proportion  of  carbohydrates  or  of  fat. 

It  is  both  right  and  natural  for  a  man  to  eat  whatever  he 
likes  and  as  much  as  he  likes,  and,  if  he  otherwise  leads  a 
healthy  life,  this  system  does  not  conduce  to  corpulency. 
Why  should  we  accuse  a  normal  function  of  being  the  cause 
of  a  pathological  process?  Obesity  is  in  all  cases  due  to 
insufficient  employment  of  the  muscles.  A  person  taking 
bodily  exercise  does  not  become  fat,  whatever  form  of  diet  he 
adopts.  I  quite  admit  that  the  tendency  to  corpulency  may 
vary  considerably  in  different  people ;  but  this  only  shows  that 
the  organs  which  constitute  half  the  weight  of  the  body  may 
not  be  suffered  to  become  atrophied  with  impunity  in  every 
case.  There  is  no  such  thing  as  a  disposition  to  stoutness 
which  may  not  be  overcome  by  muscular  work.  Show  me  a 
single  fat  field-laborer !  It  cannot  be  said  that  all  these 
people  are  badly  fed  ;  many  of  them  are  as  well  nourished  as 
it  is  possible  to  be,  and  their  diet  is  certainly  never  poor  in 
carbohydrates,  nor  often  in  fatty  matter. 

It  is  well  known  that  the  deposit  of  fat  is  encouraged  by 
the  use  of  alcohol,  for  which  we  are  at  present  unable  to  give 
a  satisfactory  explanation.  It  readily  suggests  itself  that  alco- 
hol, as  a  very  combustible  substance,  exercises  an  economizing 
effect  upon  organic  articles  of  diet,  which  are  all  capable  of 

1  Max  Rubner,  Zeitschr.  f.  Biolog.,  vol.  xxii.  p.  272  :  188^!. 


FORMATION    OF    FAT    IN    THE    ANIMAL    BODY  369 

being  converted  into  fat.  But  it  is  possible  that  alcohol  pro- 
motes the  formation  of  fat,  in  the  same  way  as  we  have  seen 
with  other  poisons,  such  as  phosphorus,  arsenic,  and  antimony 
{vide  supra,  pp.  120-121  and  363-364).  In  a  great  measure, 
the  influence  of  alcohol  on  fat-formation  may  be  attributed 
to  the  paralyzing  influence  it  exerts  upon  the  human  brain, 
causing  indolence  and  indisposition  to  bodily  exertion.  The 
therapeutics  of  corpulency  are  therefore  very  simple  :  the 
patient  must  be  prohibited  the  use  of  all  alcoholic  beverages, 
and  he  must  be  required  to  take  exercise.  In  many  cases,  to 
forbid  alcohol  is  all  that  is  required.  If  the  heart  however 
already  shows  signs  of  weakness  and  fatty  degeneration,  it  is 
necessary  to  be  cautious  in  ordering  muscular  exercise,  and 
not  to  advise  sudden  and  violent  exertion.  Corpulency  should 
not  be  met  by  a  so-called  short  cure,  such  as  mountaineering 
during  a  few  weeks  in  the  year.  The  cure  should  last  as  long 
as  life,  and  should  merely  consist  in  putting  the  muscles  to 
their  natural  use.  That  however  is  the  very  thing  the  wealthy 
patient  will  not  do,  any  more  than  he  will  renounce  his  alcohol. 
Physicians  therefore  have  devised  the  most  extraordinary 
methods  for  reducing  fat,  by  which  possibly  some  thousands 
have  been  cured  to  death.  The  absurdity  of  all  these  cures 
consists  in  trying  to  substitute  one  abnormality  for  another. 
The  physician  endeavors  to  compensate  for  insufficient  muscular 
work  by  insufficient  nourishment,  or  by  a  badly  composed 
diet,  or  even  by  causing  an  imperfect  digestion  of  the  food 
(through  administering  saline  purgatives) ;  in  other  cases,  he 
permits  the  continued  use  of  alcohol  while  withdrawing  the 
carbohydrates  and  fats. 

If  the  first  irregularity  be  entirely  and  permanently  over- 
come, it  is  unnecessary  to  interfere  in  any  other  way  with  the 
natural  course  of  the  vital  functions. 


24 


LECTURE   XXV 

lEON 

The  amount  of  iron  contained  in  the  adult  human  body  is 
not  accurately  known.  We  can  only  estimate  it  approximately 
from  the  quantities  which  I  have  found  in  the  total  organism 
of  small  mammals. 

A  mouse  gontains  100  mg.  Fe  1 

A  guinea-pig  "       52    "     "     V  per  kilo,  body-weight. 

A  rabbit  "       46    "     "    j 

It  thus  appears  that  animals  are  relatively  poorer  in  iron  as 
the  body-weight  increases,  and  that  we  must  therefore  reckon 
not  more  than  46  mg.  Fe  per  kilo,  in  man.  The  amount  of 
iron  in  a  body  weighing  70  kilos,  would  therefore  be  3.2  gr., 
and  this  is  a  maximum  value.  A  minimal  estimate  may  be 
computed  from  the  amount  of  iron  in  the  blood.  According 
to  Bischoif,  our  body  contains  7.1—7.7  per  cent,  blood,  and  in 
the  blood,  according  to  C.  Schmidt,  the  iron  amounts  to 
0.049—0.051  per  cent.  Hence  the  iron  in  the  blood  of  a  man 
weighing  70  kilos,  may  be  reckoned  at  something  between 
2.4—2.7  gr.  and  therefore  the  total  amount  in  the  body  must  be 
between  3.2  and  2.4.  This  iron  is  chiefly  contained  in  the  hem- 
oglobin of  our  blood.  We  have  therefore  to  inquire  :  From 
what  is  the  hemoglobin  formed?  It  does  not  exist  in  the 
food  of  most  vertebrates,  except  in  the  case  of  those  Carnivora 
and  omnivora  which  live  upon  other  vertebrates.  Among  the 
invertebrates  there  are  only  a  very  few  which  contain  a  small 
quantity  of  hemoglobin  in  certain  tissues.  The  majority  of 
the  vertebrates  must  therefore  form  their  hemoglobin  from 
other  compounds  of  iron,  the  nature  of  which  we  will  now 
consider. 

Until  recently  little  investigation  has  been  made  on  this 
subject.  As  oxid  of  iron  was  found  in  the  ash  of  all  articles 
of  diet,  it  was  assumed  that  hemoglobin,  which  is  well  known 
to  be  a  compound  proteid,  was  formed  by  synthesis  from  oxid 
of  iron  and  proteid. 

It  is  difficult  to  understand  how  such  a  theory  could  have 

370 


ißON  371 

been  universally  adopted  at  a  time  when  Liebig's  doctrine  of 
the  universal  antithesis  in  the  metabolism  of  plants  and  animals 
prevailed.  As  is  well  known,  Liebig  had  taught  that  synthetic 
changes  could  only  be  carried  out  in  plants,  the  animal  body 
being  able  to  eifect  only  disintegrative  changes.  It  is  true 
that  this  theory  was  shortly  afterwards  overthrown  by  Köhler's 
discovery  of  the  synthesis  of  hippuric  acid  in  the  animal  body. 
But  hippuric  acid  is  relatively  a  very  simple  compound  ;  it 
contains  only  9  atoms  of  carbon  in  the  molecule,  whereas 
hemoglobin  has  at  least  700.  It  is  therefore  inconceivable 
how  anyone  could  ever  imagine  that  such  a  complex  com- 
pound could  be  produced  in  our  body ;  that  moreover  the 
inorganic  iron  should  combine  with  its  32  atoms  of  carbon 
to  form  so  stable  a  compound  as  hematin,  which  is  united 
with  proteid  in  the  hemoglobin  molecule.  The  iron  cannot  be 
separated  from  the  hematin  even  with  the  strongest  reagents. 
It  cannot  be  detected  in  the  hematin  by  means  of  ammonium 
sulphid ;  it  is  not  split  oif  on  boiling  with  alkalies  or  most 
acids. 

The  universal  acceptance  of  this  doctrine  concerning  the 
synthesis  of  hemoglobin  from  oxid  of  iron  and  proteid  would 
be  quite  incomprehensible  were  it  not  for  the  success  which 
physicians  think  they  have  achieved  in  the  treatment  of  chlorosis 
by  the  administration  of  inorganic  preparations  of  iron.  In 
chlorosis  the  amount  of  hemoglobin  in  the  body  is  diminished  ; 
after  iron  salts  have  been  taken  it  is  increased.  Hemoglobin  is 
an  iron  compound.  What  could  be  more  natural  than  the  con- 
clusion that  the  iron  administered  was  used  to  form  the  hemo- 
globin? Nevertheless  this  conclusion  seems  to  have  been 
erroneous. 

Later  investigation  has  shown  that  the  iron  given  by  physi- 
cians in  chlorosis,  with  the  object  of  making  hemoglobin  from 
it,  is  probably  not  absorbed  at  all. 

So  far  as  I  am  aware,  the  first  experiments  which  threw  a 
doubt  upon  the  absorbability  of  preparations  of  iron  were  pub- 
lished by  Yincenz  KletzinskyMn  1854.  His  communication 
however  is  short  and  lacking  in  precision ;  the  figures  appear 
so  little  trustworthy  that  no  notice  was  taken  of  the  work. 
It  was  quite  unknown  to  me  at  the  time  that  I  undertook  my 
experiments  on  iron.  Kletzinsky  found  that,  in  seven  ex- 
periments on  himself,  metallic  iron,  oxid  of  iron,  sulphid  of 
iron,  iodid  of  iron,  acetate,  lactate,  and  malate  of  iron  could 
be  recovered  without  loss    from  the  feces.     The  same  result 

^  V.  Kletzinsky,  Zeitschr.  d.  k.  k.  Gesellsch.  d.  Aerzte  s.  Wien.,  Jahrgang  10, 
vol.  ii.  pp.  281-289 :  1854. 


372  LECTURE    XXV 

was  obtained  from  careful  experiments  carried  out  by  E.  W. 
Hamburger  ^  with  ferrous  sulphate  on  the  dog,  and  by  Marfori  ^ 
in  Schmiedeberg's  laboratory  with  lactate  of  iron  on  the  same 
animal. 

The  inorganic  preparation  of  iron  administered  by  the 
mouth  does  not  enter  into  the  urine,  which  in  a  normal  state 
contains  an  inappreciable  quantity  of  this  substance.  In  ex- 
periments on  animals  in  which  inorganic  compounds  of  iron 
were  given  internally,  the  amount  of  iron  in  the  urine  rose 
slightly  only  if  the  doses  were  so  large  or  were  continued  so 
long  as  to  render  it  probable  that  the  intestinal  epithelium  was 
inflamed.^ 

We  might  conclude  from  these  researches  that  inorganic 
preparations  of  iron  are  not  absorbed  from  the  normal  intestine. 
But  there  is  still  an  objection  which  must  be  refuted,  viz.,  the 
possibility  that  the  iron  taken  may  be  absorbed,  but  may  be 
again  excreted  in  the  intestine.  This  objection  has  the  more 
weight  owing  to  the  fact  that  the  iron  absorbed  from  the  food 
and  set  free  in  the  normal  process  of  metabolism  takes  this 
path.  This  may  be  seen  in  fasting  animals.  The  iron  which 
appears  in  the  feces  of  fasting  animals  cannot  come  from  un- 
absorbed  iron,  but  must  have  been  excreted  into  the  intestine. 
Bidder  and  Schmidt*  found  6  to  10  times  more  iron  in  the  feces 
than  in  the  urine  of  fasting  cats.  The  same  result  was  obtained 
in  recent  experiments  on  the  metabolism  of  fasting  men  ;  7  to  8 
mg.  iron  were  found  daily  in  the  feces.^ 

As  regards  the  path  by  which  the  iron  reaches  the  intestine, 
we  can  only  say  with  certainty  that  it  is  not  by  way  of  the  bile, 
since  the  latter  contains  almost  unweighable  amounts  of  this 
substance.  It  is  therefore  probable  that  the  main  bulk  of  the 
iron  is  eliminated  through  the  intestinal  wall.  The  justice  of 
this  assumption  is  most  clearly  shown  by  an  experiment  of 
Fritz  Voit.^     In  the  dog  he  isolated  a  length  of  small  intestine 

^  E.  W.  Hamburger,  Zeitschr.  f.  physiol.  Chem.,  vol.  ii.  p.  191 :  1878. 

2  Pio  Marfori,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxix.  p.  212  :  1892. 

^  In  many  of  the  most  recent  experiments  on  the  administration  of  inorganic 
forms  of  iron,  this  substance  has  been  found  in  larger  quantities  in  the  intestinal 
wall,  in  the  liver,  in  the  chyle,  &c.  But  in  all  these  cases  the  small  animals  were 
given  too  large  amounts  of  iron  in  proportion  to  their  body-weight.  Vide  H.  W. 
F.  C.  Woltering,  Zeitschr.  f.  physiol.  Chem.,  vol.  xxi.  p.  186:  1895;  J.  Gaule, 
Deutsch,  med.  Wochenschr.,  Nos.  19  and  24:  1896;  W.  S.  Hall,  Arch.  f.  Anat. 
u.  Physiol.,  p.  49:  1896;  Hochhaus  u.  Quincke,  Arch.  f.  exper.  Path.  u. 
Pharm.,  vol.  xxxvii.  p.  159  :  1896. 

*  Bidder  u.  Schmidt,  "Die  Verdauungssäfte  u.  d.  Stoffwechsel,"  Mitau  u. 
Leipzig,  p.  411 :  1852. 

*  C.  Lehmann,  Fr.  Mueller,  J.  Munk,  H.  Senator  u.  N.  Zuntz,  Virchow's 
Arch.,  vol.  cxxxi.  Suppl.,  pp.  18  and  &7  :  1893. 

«  Fritz  Voit,  Zeitschr.  f.  Biolog.,  vol.  xxix,  p.  325  :  1893. 


lEON  373 

with  the  same  procedure  as  in  Thiry's  experiment  (see  p.  172), 
the  only  difference  being  that  after  the  isolated  piece  of  intes- 
tine had  been  cleansed,  both  ends  were  sewn  up ;  the  piece  of 
intestine  was  then  replaced,  and  the  abdominal  wound  closed. 
The  animals  were  fed  upon  meat  for  three  weeks,  at  the  end  of 
which  time  they  were  killed,  and  the  iron  was  estimated  both 
in  the  contents  of  the  isolated  length  of  intestine  and  in  the 
feces  which  had  been  formed  in  the  remaining  part  of  the  intes- 
tines during  the  period  of  the  experiment.  Per  unit  area  of 
mucous  membrane,  as  much  iron  was  found  in  the  isolated  coil 
as  in  the  feces  obtained  from  the  remaining  intestine. 

If  reduced  iron  were  added  to  the  meat  diet,  the  proportion 
of  iron  in  the  contents  of  the  isolated  piece  was  not  increased. 
From  these  experiments  Voit  concludes  that  the  iron  contained 
in  normal  diet  is  absorbed  by  the  intestinal  wall,  and  again 
excreted  through  the  intestinal  wall ;  and  that,  on  the  other 
hand,  the  inorganic  preparations  of  iron  administered  artificially 
are  not  absorbed  to  any  appreciable  extent. 

The  objection  to  this  last  deduction  is  that  the  inorganic 
iron  when  absorbed  may  be  eliminated  only  in  certain  sections 
of  the  intestinal  tube,  and  that  this  particular  isolated  portion 
did  not  have  that  power.  This  question  may  therefore  be  re- 
garded as  still  undecided. 

But  if  we  accept  the  conclusion  that  the  inorganic  forms  of 
iron  are  not  absorbed,  it  follows  that  our  food  must  contain  other 
combinations  of  organic  iron,^  which  are  assimilable  and  serve 
as  the  precursors  of  hemoglobin.  I  have  sought  to  discover  the 
nature  of  these  compounds,  using  the  yolk  of  egg  as  the  basis 
for  my  experiments.^  Yolk  of  egg  does  not  contain  any 
hemoglobin  ;  but  it  must  contain  a  precursor  of  this  substance, 
since  hemoglobin  is  found  in  the  egg  during  incubation  without 
the  introduction  of  any  material  from  without.  I  succeeded  in 
isolating  this  precursor  in  a  quantity  sufficient  for  an  exact  re- 
search. If  the  yolk  of  hens'  eggs  be  extracted  with  alcohol 
and  ether,  no  iron  passes  out  with  the  extract,  but  remains  in 
the  residue,  which  forms  one-third  of  the  dried  substance  of  the 
yolk  and  consists  of  proteids  and  nucleins.  The  large  amount  of 
iron  in  this  residue  does  not  occur  in  the  form  of  a  salt,  as  may 
be  proved  by  the  fact  that  it  cannot  be  extracted  with  alcohol 
containing  hydrochloric  acid ;  whereas  all  salts  of  iron,  whether 
in  combination  with  inorganic  or  organic  acids — and  amongst 

*  Kletzinsky,  loc.  cit.,  ascribes  this  theory  in  the  first  place  to  Hannon,  whose 
writings  are  not  accessible  to  me.  But  the  existence  of  organic  compounds  of  iron 
in  our  food  has  in  nowise  been  proved  by  either  of  these  authors. 

2  G.  Bunge,  Zeitschr.  f.  physiol.  Chem.,  vol.  ix.  p.  49  :  1884. 


374  LECTURE    XXV 

these  we  must  reckon  proteids — at  once  yield  their  iron  to  the 
acid  alcohol.  The  remainder  of  the  yolk  of  egg  which  is  in- 
soluble in  ether,  dissolves  readily  in  very  dilute  (1  per  M.) 
hydrochloric  acid.  If  to  this  solution  tannic  or  salicylic  acid 
be  added,  a  white  precipitate  is  thrown  down  ;  but  if  even  the 
slightest  trace  of  ferric  chlorid  be  shaken  up  with  this  solution, 
and  it  be  now  treated  with  tannic  or  salicylic  acid,  it  turns 
either  of  a  blue  or  red  color  respectively. 

Iron  occurs  in  yolk  of  egg  as  a  nucleo-albumin.  In  artificial 
gastric  digestion  of  yolk  of  egg,  the  proteids  are  converted  into 
peptones,  and  the  iron  remains  in  the  indigestible  insoluble 
residue,  the  nuclein.^  As  in  the  case  of  the  original  compound, 
the  iron  in  this  nuclein  cannot  be  extracted  by  hydrochloric 
acid  alcohol.  The  iron  is  slowly  split  off  by  a  watery  solution 
of  hydrochloric  acid,  and  more  quickly  according  to  the  con- 
centration of  the  acid. 

The  nuclein-iron  compound  is  soluble  in  ammonia.  If  to  the 
ammoniacal  solution  some  potassium  ferrocyanid  and  excess 
of  hydrochloric  acid  be  added,  a  precipitate  is  produced,  which 
is  at  first  white,  and  gradually  becomes  blue,  the  change  occur- 
ring more  rapidly  as  the  concentration  of  the  hydrochloric 
acid  is  increased.  If,  instead  of  the  ferrocyanid,  potassium 
ferricyanid  and  hydrochloric  acid  be  added  to  the  ammoniacal 
solution,  the  precipitate  remains  white.  The  iron  is  therefore 
split  off  from  the  organic  compound  as  ferric,  and  not  as 
ferrous,  oxid. 

If  to  the  ammoniacal  solution  of  the  iron-nuclein  compound 
a  drop  of  ammonium  sulphid  be  added,  no  change  of  color 
is  at  first  observed :  after  a  little  time,  however,  the  solution 
takes  a  slightly  greenish  tinge,  which  increases  in  intensity 
until  finally  the  next  day  it  becomes  black  and  opaque.  The 
change  in  color  proceeds  with  greater  rapidity  according  to 
the  amount  of  ammonium  sulphid  added.  Ammoniacal  solu- 
tions of  artificial  albuminates  of  iron  change  color  almost  in- 
stantaneously when  treated  with  ammonium  sulphid. 

'  A  nuclein  was  first  prepared  by  Miescher  from  the  yolk  of  egg.  His  method 
of  preparation  was  however  different  from  mine,  and  I  imagine  that  the  iron  had 
been  mostly  split  off  from  the  compound  by  the  action  of  the  hydrochloric  acid 
in  the  gastric  juice.  Otherwise  the  large  amount  of  iron  could  not  have  escaped 
Mieseher's  notice.  In  my  preparation  the  pepsin  ferment  acted  only  a  very  short 
time  on  the  solution  of  the  nucleo-albuminates  in  very  dilute  hydrochloric  acid.  In 
Mieseher's  preparation  the  yolk  of  egg,  after  extraction  with  ether  and  alcohol, 
was  allowed  to  digest  for  18  to  24  hours  in  gastric  juice,  containing  3  to  4  per  mille 
HCl  (10  ccm.  of  fuming  HCl  to  1  liter  of  water),  at  a  temperature  of  40°  C.  In 
my  method  of  preparation  the  hydrochloric  acid  amounted  only  to  a  little  over 
1  per  mille,  and  the  solution  was  kept  at  body  temperature  only  until  the  iron- 
nuclein  compound  began  to  separate  out  of  the  solution  as  a  cloudy  precipitate. 
(  Vide  Miescher,  in  Hoppe-Seyler's  Med.  chem.  Unters.,  pp.  454  and  504:  1871.) 


IRON 


375 


Iron  therefore  is  more  closely  combined  in  the  nuclein  of 
yolk  of  egg  than  in  the  iron  albuminates,  but  far  more  loosely 
than  in  hematin,  in  which  it  cannot  be  detected  by  means  of 
the  ordinary  reagents. 

The  elementary  analysis  of  the  iron-nuclein  compound  gave 
the  following  composition  : 


C 42.11 

H 6.08 

N 14.73 

S 0.55 


P 

Fe 

O 


5.19 

0.29 

31.05 


This  compound  is  undoubtedly  the  precursor  of  hemoglobin, 
since  there  are  no  other  iron  compounds  present  in  any  quan- 
tity in  yolk  of  egg.  I  have  therefore  suggested  that  this 
substance  should  be  termed  hematogen  (blood-forming).*  If 
we  imagine  the  phosphorus  to  have  been  split  off  from  the 
hematogen  as  phosphoric  acid,  we  get  a  molecule  containing 
the  same  amount  of  iron  as  hemoglobin.  The  hemoglobin  of 
hen's  blood  possesses  0.34  per  cent.  Fe.^ 

Following  the  same  method  by  which  I  prepared  hemato- 
gen from  hens'  eggs,  an  exactly  similar  compound  was  obtained 
from  carps'  eggs  in  Kossel's^  laboratory.  The  elementary 
analysis  of  this  compound  gave  the  following  figures  : 


Preparation  I. 

Preparation  II 

c 

48.0 

47.8 

H 

7.2 

7.2 

N 

14.7 

12.7 

S 

0.30 

— 

P 

Fe 

2.4 

2.9 
0.25 

That  hematogen  may  be  absorbed  and  assimilated  is  shown 
by  the  experiments  carried  out  by  C.  A.  Socin  *  in  my  labora- 
tory. Mice  fed  on  an  artificial  diet,  which  contained  no 
compound  of  iron  except  hematogen,  lived  for  a  hundred  days, 
and  gained  in  weight. 

In  our  most  important  articles  of  vegetable  diet  the  iron 
is  also  united  loosely  with  organic  substances  as  in  hematogen. 

1  The  name  hemoglobinogen  would  be  more  suitable  but  too  lengthy.  The 
name  hematogen  has  been  objected  to  on  the  score  that  it  already  occurs  in 
medical  nomenclature  as  an  adjective:  "hematogenic  icterus."  But  as  recent 
research  has  shown  that  there  is  no  such  thing  as  hematogenic  icterus,  we 
shall  soon  be  able  to  do  without  the  term  altogether. 

2  A.  Jaquet  (Bunge's  laboratory),  Zeitschr.  f.physiol.  Chem.,  vol.  xiv.  p.  289 : 
1889. 

^  G.  Walter,  Zeitschr,  f.  physiol.  Chem.,  vol.  xv.  p.  489  :  1891. 
*  C.  A.  Socin  (Bunge's  laboratory),  ^eitecAr.  /.  physiol.  Chem.,  vol.  xv.  p.  93  : 
1891. 


376 


LECTURE   XXV 


But  the  attempt  to  isolate  these  compounds  is  attended  with 
much  greater  difficulty,  since  several  different  kinds  are  here 
met  with. 

I  found  it  particularly  hard  to  prepare  iron-compounds 
from  milk,  because  not  only  does  the  iron  occur  in  union 
with  various  substances,  but  it  is  also  present  in  very  small 
quantities.  A  glance  at  the  following  table  ^  will  show  that 
there  is  less  iron  in  milk  than  in  almost  any  other  article  of 
food : 


OiJ^E  Hundred  Grms.  Dried  Substance  Contain  the  Following 
Amounts  of  Iron  in  Milligrammes. 


Blood  serum  .  .  . 
White  of  hen's  egg 

Eice  

Pearl  barley  .  .  . 
Wheat  flour  (sifted) 
Cow's  milk      .    .    . 


0 

Trace 

1.0-2.0 

1.4-1.5 

1.6 

2.3 

Human  milk 2.3-3.1 

Dog's  milk 3.2 

Figs      3.7 

Raspberries 3.9 

4.3 
4.5 
4.5 
4.9 
4.9 
5.5 
5.7 
6.4 
6.2-6.6 


Hazel  nuts  (kernel  only).    . 

Barley      

Cabbage  (inside  yellow  leaves) 

Eye 

Almonds  (peeled)      .... 

Wheat      

Bilberries 

Potatoes 


Cherries  (black, without  stones)  7.2 

Beans  (white) 8.3 

Carrots 8.6 

Wheat-bran 8.8 

Strawberries 8.6-9.3 

Linseed    ........       9.5 

Almonds  (brown  skins)    .    .       9.5 
Cherries  (red,  without  stones)  10 
Hazel  nuts  (brown  skins)    .      13 
Apples     ......  13 

Dandelion  leaves  .    .  14 

Cabbage  (outer  green  leaves)    17 

Beef 17 

Asparagus 20 

Yolk  of  egg 10-24 

Spinach 33-39 

Pig's  blood 226 

Hematogen      .......     290 

Hemoglobin 340 


This  fact  caused  me  surprise,  as  ä  priori  I  had  anticipated 
the  contrary,  viz.,  that  milk,  being  the  exclusive  food  of  the 
growing  organism  which  is  always  increasing  its  blood-supply, 
would  contain  more  iron  than  the  food  of  full-grown  animals 
which  merely  have  to  maintain  their  previous  store  of  iron. 
The  small  amount  of  iron  in  the  milk  is  the  more  remarkable 
since  all  other  inorganic  food-stuifs  are  contained  in  milk  in  just 
the  proportion  in  which  they  are  needed  for  the  growth  of  the 
sucking  animal. 

1  The  original  sources,  from  which  all  the  analyses  in  this  table  are  taken,  are 
given  by  G.  Bunge,  Zeitschr.  f.  physiol.  Chem.,  vol.  xvi.  p.  174:  1891 ;  and  by 
E.  Häusermann  (Bunge's  laboratory),  Zeitschr.  f.  physiol.  Chem.,  vol.xxiii.  p. 
586:  1897. 


IRON  377 

On,e  Hundred  Parts  by  Weight  of  Ash  Contain  : 

In  New-born  Puppy.         Dog's  Milk. 

K2O 11.42  14.98 

NajO 10.64  8.80 

CaO              29.52  27.24 

MgO 1.82  1.54 

FeA       0.72  0.12 

P2O5 39.42  34.22 

CI 8.35  16.90 

With  the  exception  of  the  iron,  the  relative  proportion  of 
the  remaining  constituents  in  the  ash  is  almost  identical.  The 
object  of  this  uniformity  is  evidently  to  ensure  the  greatest 
possible  economy.  The  maternal  organism  gives  nothing 
which  cannot  be  utilized  by  the  oifspring.  An  •  excess  of  any 
constituent  would  be  wasted.  This  marvellous  adaptation  of 
means  to  an  end  appears  however  to  be  rendered  futile  by  the 
small  amount  of  iron  in  the  ash  of  milk  :  it  is  six  times  less 
than  that  in  the  ash  of  the  sucking  animal.  According  to  this, 
the  maternal  organism  would  seem  to  part  with  six  times  too 
much  of  the  remaining  constituents  to  its  offspring.  Appa- 
rently only  one-sixth  can  be  employed  to  build  up  the  organs, 
and  the  remaining  five-sixths  are  thrown  away  ! 

The  explanation  of  this  contradiction  is  that  the  young 
animal  contains  at  birth  a  large  store  of  iron  for  the  growth  of 
its  tissues.  In  a  series  of  estimations  of  iron  in  the  total 
organism  of  young  dogs,  cats,  and  rabbits,  I  have  shown  that 
the  amount  of  iron  is  the  highest  at  birth,  and  that  it  gradually 
diminishes  afterwards.^  At  least  five  times  more  iron  is  found 
in  the  liver  of  new-born  than  in  that  of  full-grown  animals. 
In  the  same  way  the  other  tissues  must  possess  their  store  of 
iron  which  can  be  drawn  upon  to  meet  the  rapid  development 
of  the  blood. 

The  advantage  of  this  arrangement  seems  to  be  as  follows  : 
The  assimilation  of  organic  compounds  of  iron  is  obviously 
attended  with  great  difficulty,  hence  the  maternal  organism 
uses  up  its  acquired  store  with  the  greatest  economy.  The 
amount  which  must  be  conveyed  to  the  infant  organism  can 
reach  it  in  two  ways  :  through  the  placenta  and  through  the 
mammary  glands.  The  former  way  is  preferred  as  the  more 
secure.  If  the  main  proportion  of  the  organic  compounds  of 
iron  was  conveyed  by  the  mammary  gland,  it  might  become  a 
prey  to  bacteria  in  the  alimentary  canal  and  before  absorption 
had  begun.  But  if  it  reaches  the  fetus  through  the  placenta,  its 
safety  is  assured. 

^  G.  Bunge,  Zeitschr.  f.  physiol.  Chem.,  vol.  xvi.  p.  177  :  1891,  and  vol.  xvii. 
p.  63 :  1892. 


378 


LECTURE    XXV 


In  the  following  table  ^  I  give  the  figures  for  the  amount 
of  iron  in  young  rabbits  and  guinea-pigs. 


RABBITS. 

(Age  of  the  animals.) 


Mg.  Fe 
to  100  grins, 
body-weight. 

Embryos  arranged  according  J  nV 
to  increasing  body-weight.  1  o'a 


1  hour  after  birth 
1  day 

4  days 

5  " 

6  " 

7  " 
11  " 
13  " 
17  " 
22  " 
24  " 
27  " 
41     " 

45  " 

46  " 
74     " 


18.2 
13.9 
9.9 
7.8 
8.5 
6.0 
4.3 
4.5 
4.3 
4.3 
3.2 
3.4 
4.5 
4.2 
4.1 
4.6 


GUINEA-PIGS. 

(Age  of  the  animals.) 


Embryos , 


6  hours  after  birth 

U  days  " 

3        u  a  II 

K             li  <(  (( 

9      "  "  " 

15      "  "  " 

22      "  "  " 

25      "  "  " 

53      "  "  " 


Mg.  Fe 
to  100  grms. 
body-weight. 

r4.6 

4.4 
5.6 
5.3 
5.0 
6.0 
5.4 
5.7 
5.7 
4.4 
4.4 
4.4 
4.5 
5.2 


I  have  ascertained  from  repeated  and  continued  investiga- 
tion of  the  gastric  contents  that  young  rabbits  are  nourished 
during  the  first  fortnight  exclusively  on  the  mother's  milk. 
About  the  middle  of  the  third  week  they  begin  to  take  vege- 
table food  as  well  as  the  milk,  and  in  the  fourth  week  the 
stomach  contains  principally  vegetable  matter.  As  the  above 
figures  show,  the  fourth  week  is  the  time  when  the  store  of 
iron  has  become  used  up  and  the  amount  of  iron  in  proportion 
to  the  body-weight  has  reached  its  minimum.  With  the 
commencement  of  a  vegetable  dietary  rich  in  iron,  the  amount 
of  this  substance  in  the  body  again  begins  to  rise. 

The  case  of  guinea-pigs  is  very  different.  These  animals 
begin  by  eating  vegetable  food  from  the  first  day  and  select  by 
preference  the  leaves  which  are  very  rich  in  iron,  and  during 
the  subsequent  days  milk  plays  but  a  subordinate  part  com- 
pared to  this  form  of  food.  And  correspondingly  we  find  that 
(as  may  be  seen  from  the  above  figures)  guinea-pigs  have  at 
birth  a  very  small  store  of  iron  in  their  organs.  Thus  in  these 
two  nearly  related  animal  species,  Nature  herself  has  made  an 
experimentum  crucis,  which  confirms  my  conception  concerning 
the  significance  of  the  store  of  iron  provided  for  new-born 
animals. 

Very  little  iron  is  assimilated  from  the  milk   during  the 


^  G.  Bunge,  idem. 


IRON  379 

suckling  period.  In  the  young  rabbit  the  absolute  amount  of 
iron  remains  nearly  constant,  whereas  the  body  increases  in 
weight  sixfold  by  the  end  of  the  fourth  week.  The  relative 
proportion  of  iron  therefore  falls  to  one-sixth,  as  reference  to 
the  above  table  will  show.  The  animals  at  this  time  appear 
to  be  already  anemic.  But  they  now  begin  to  take  food  con- 
taining abundance  of  iron,  when  the  amount  of  this  substance 
at  first  rises.  Subsequently  the  absolute  quantity  of  assimilated 
iron  grows  in  proportion  to  the  body-weight,  and  the  relative 
amount  remains  nearly  constant.  If  the  attempt  were  made 
to  feed  the  young  animals  exclusively  with  milk  after  the 
period  of  suckling  had  elapsed,  they  would  certainly  become 
anemic. 

This  condition  of  anemia  has  been  utilized  by  me  to  decide 
the  question  as  to  the  assimilability  of  inorganic  iron.  At  the 
end  of  lactation,  the  young  animals  were  fed  entirely  on  milk, 
or  on  milk  and  rice.  Rice,  as  we  may  seß  from  the  table,  is 
even  poorer  in  iron  than  milk.  One  half  of  the  animals  em- 
ployed in  this  experiment  received  in  addition  to  this  food,  a 
small  quantity  of  ferric  chlorid  daily.  After  this  diet  had 
been  given  from  one  to  three  months,  and  the  animals  had 
doubled  their  weight,  they  were  killed  and  the  amount  of 
hemoglobin  in  the  total  body  was  estimated,  as  well  as,  in  the 
case  of  small  animals,  the  amount  of  iron. 

In  this  manner  E.  Häusermann  carried  out  experiments  in 
my  laboratory  on  24  rats,  17  rabbits,  14  dogs,  and  3  cats.  The 
rats  all  became  highly  anemic ;  for  at  the  end  of  the  experi- 
ment the  percentage  of  hemoglobin  was  diminished  to  about 
half  that  of  animals  from  the  same  litter  which  had  received 
their  normal  food  —  meat,  flies,  yolk  of  egg,  fruit,  vegetables. 
The  rats,  which  had  taken  ferric  chlorid  in  addition  to  the  milk 
and  rice,  contained  no  more  hemoglobin  than  those  which  had 
received  milk  and  rice  only.  Moreover  the  amount  of  iron 
was  in  each  case  the  same.  In  one  experiment  alone,  in  which 
the  addition  of  ferric  chlorid  was  continued  for  three  months, 
was  the  iron  found  to  be  double  as  much  in  the  animals  which 
received  it  as  in  those  which  had  only  milk  and  rice.  But  here 
again  the  proportion  of  hemoglobin  remained  the  same  in  both 
instances.  We  thus  see  that  some  iron  is  absorbed  if  small 
doses  of  iron  are  persisted  in  for  a  long  time,  as  well  as  if 
large  amounts  be  suddenly  administered.  But  this  inorganic 
iron,  when  absorbed,  is  not  utilized  in  the  formation  of  hemo- 
globin to  any  appreciable  extent,  but  remains  unused  in  the 
tissues.  Whether  inorganic  iron  was  absorbed  in  the  ex- 
periments, which  lasted  only  from  one  to  two  months,  cannot 


380  LECTURE    XXV 

be  decided :  it  is  possible  that  same  of  it  was  absorbed  and  was 
again  eliminated  in  the  same  degree.  Certainly  no  storing  up 
nor  increase  of  iron  could  be  detected  in  the  whole  organism. 

The  experiments  on  rabbits  gave  less  decisive  results :  the 
average  proportion  of  hemoglobin  in  the  animals  that  received 
iron  was  somewhat  higher  than  that  in  the  animals  which  were 
fed  on  milk  and  rice  only.  But  if  the  great  individual  differ- 
ences between  various  animals  be  taken  into  consideration,  I 
do  not  think  we  must  ascribe  too  much  importance  to  this 
slight  divergence.  At  any  rate  the  amount  of  hemoglobin  in 
the  control  animal,  which  received  its  normal  diet — fresh  green 
cabbage,  bran,  etc. — was  nearly  twice  as  high  as  in  the  animal 
which  received  the  iron. 

The  experiments  on  dogs  were  not  attended  with  decisive 
results.  Dogs  are  not  suitable  animals  for  these  experiments 
owing  to  their  individual  differences.  Moreover  the  growth  of 
these  animals  after  the  period  of  lactation  is  at  a  much  slower 
rate,  and  their  appetite  so  enormous  that  they  might  be  readily 
able  to  assimilate  sufficient  hemoglobin  even  from  a  material  so 
poor  in  iron  as  milk,  while  their  appetite  remained  normal. 
Häusermann  found  the  largest  proportion  of  hemoglobin  in  a 
dog  which  had  been  fed  exclusively  with  milk.  The  animals 
which  received  ferric  chlorid  in  addition  to  a  milk  diet  certainly 
contained  no  more  hemoglobin  than  animals  from  the  same 
litter  which  were  fed  on  meat  and  bones.  Cloetta^  carried  out 
some  experiments  on  the  same  principle  as  ours,  and  came  to  the 
conclusion  that  iron  was  assimilated  in  its  inorganic  form.  We 
are  not  at  present  in  a  position  to  corroborate  this  statement. 

Häusermann  further  conducted  a  research  on  the  question 
as  to  whether  the  hemoglobin  of  the  food  was  assimilable.  It 
appeared  that  young  rats,  which  were  given  dried,  powdered 
hemoglobin  in  addition  to  milk  and  rice,  formed  twice  as  much 
hemglobin  as  the  animals  from  the  same  litter,  which  received 
milk  and  rice  alone.  The  hemoglobin  of  the  food  therefore 
appears  to  be  absorbed  and  assimilated.  This  experiment  with 
hemoglobin  was  however  performed  on  only  two  animals,  and  I 
intend  therefore  to  repeat  it. 

In  order  to  obviate  misapprehension,^  I   may  be  allowed 

^  M.  Cloetta,  Arch.  f.  exper.  Path.  it.  Pharm.,  vol.  xxviii.  p.  161 :  1897. 

'  My  previous  publications  on  the  iron  question  have  been  continually  mis- 
represented by  the  medical  press.  In  particular  the  statements  which  were 
made  by  me  at  the  Clinical  Congress  at  Munich  in  the  spring  of  1895  have  been 
reported  in  quite  a  contrary  sense.  At  the  Congress  I  gave  an  account  of  the 
present  state  of  the  question  from  an  objective  standpoint,  reserving  my 
judgment,  speaking  sceptically  and  affirming  nothing.  Comp.  Verhandl.  des 
Congresses  f.  inn,.  Med.,  Cong,  xiii.,  Wiesbaden,  Bergmann,  pp.  133  and  191 : 


IRON  381 

to  shortly  recapitulate  the  results  of  the  investigations  on  the 
absorption  and  assimilation  of  inorganic  iron  : 

1.  So  far  it  has  not  been  proven  that  any  part  of  the 
inorganic  preparations  of  iron  given  in  the  small  quantity 
(0.1—0.2  grm.  Fe  per  diem)  Avhich  is  necessary  in  order  to 
avoid  digestive  disturbances,  is  absorbed  either  in  man  or  in 
the  smaller  animals,  to  which  correspondingly  less  iron  can  be 
administered.  We  must  however  concede  the  possibility  that 
small  amounts  may  be  absorbed. 

2.  If  large  quantities  of  iron  be  given,  or  if  the  administra- 
tion of  small  doses  be  continued  over  a  long  period,  part  of  the 
iron  passes  the  intestinal  wall.  But  it  cannot  be  ascertained 
whether  this  iron  is  assimilated,  although  such  a  possibility 
cannot  be  denied. 

3.  Even  if  the  assimilation  of  inorganic  preparations  of 
iron  be  granted,  it  is  indisputable  that  the  iron  which  exists  in 
normal  food  in  the  form  of  organic  compounds  is  far  more 
readily  and  more  completely  absorbed. 

Should  further  research  show  that  inorganic  iron  is  utilized 
in  the  production  of  hemoglobin,  the  fact  would  be  of  the 
greatest  theoretical  interest.  It  would  furnish  fresh  proof  that 
syntheses  occur  as  complex  in  the  animal  as  in  the  vegetable 
cell.  Hitherto  scientific  men,  steeped  in  Liebig's  doctrine,  have 
ascribed  too  little  power  to  the  animal  cell.  But  even  if  the 
assimilation  of  inorganic  iron  was  a  proved  fact,  it  would  have 
no  importance  in  medical  practice  since,  as  our  experiments  show, 
the  iron  required  for  the  formation  of  hemoglobin  is  much 
more  readily  and  plentifully  assimilated  from  the  organic  iron- 
compounds  of  our  normal  dietary.  Hence  there  is  in  no  case 
any  reason  to  prescribe  preparations  of  iron  for  the  production 
of  hemoglobin  in  people  who  can  take  their  natural  food  with 
a  good  appetite. 

It  is  quite  another  question  as  to  whether  anemic  patients 
should  be  given  preparations  of  iron,  not  indeed  as  material  for 
conversion  into  hemoglobin,  but  in  order  to  influence  the 
formation  of  blood  in  some  indirect  way.  That  these  prepara- 
tions may  have  such  an  effect  cannot  be  denied,  although  there 
is  so  far  no  adequate  proof  on  the  matter.  It  is  not  sufficient 
evidence  to  say  that  the  experience  has  been  made ;  we  must 
know  how  it  has  been  done.  Where  are  the  statistics  ?  Where 
are  the  control  experiments  ?  ^ 

1895.    I  request  that  for  the  future  I  may  be  attacked  only  for  what  I  have  said, 
and  not  for  what  I  have  never  said. 

^  Compare  my  critique  of  the  therapeutics  of  iron  in  the  Verhandl.  des  Con- 
gresses f.  inn.  Med.,  Congr.  xiii.,  Wiesbaden,  Bergmann,  pp.  143-147  and  191  : 
1895. 


382  LECTURE   XXV 

If  thus  all  previous  experimentation  teaches  us  decisively 
that  iron  is  most  surely  and  abundantly  assimilated  from  our 
natural  food,  it  follows  that  it  is  highly  desirable  for  us  to 
know  the  proportion  of  iron  contained  in  the  various  articles  of 
our  diet.  This  knowledge  will  be  of  the  greatest  value  both  as 
a  weapon  and  as  a  prophylactic  against  poorness  of  blood.  Let 
us  therefore  again  glance  at  the  table  on  p.  376.  It  is  a  very 
surprising  fact  that,  next  to  milk,  the  cereals,  which  are  the 
most  important  articles  of  vegetable  food,  contain  the  least 
iron,  that  is  to  say,  in  the  form  in  which  they  are  generally 
consumed,  when  deprived  of  their  husks,  the  so-called  bran. 
Rice,  as  it  comes  into  the  market,  is  already  deprived  of  its 
husk  ;  it  does  not  correspond  to  barley  or  wheat  corn  but  to 
pearl  barley  or  wheat  flour.  In  sifting  the  flour,  the  husks, 
the  so-called  bran,  are  separated  from  the  flour.  From  the 
table  we  see  that  the  cereals,  when  freed  from  their  husks, 
contain  only  half  as  much  iron  as  milk.  The  iron  of  the  cereals 
exists  in  the  husks.  Whole  wheat-meal  therefore  contains  five 
times  as  much  iron  as  the  ordinary  wheat-flour. 

This  shows  how  irrationally  anemic  people  are  fed.  We 
may  take  as  an  instance  the  poor  bloodless  seamstresses,  who 
eat  white  bread  and  drink  tea  !  With  the  aid  of  all  our 
chemical  knowledge  we  could  not  give  to  animals  which  we 
wished  to  make  anemic  any  food  with  less  iron  it  ! 

It  would  be  very  interesting  to  ascertain  experimentally 
whether  the  iron  compounds  in  the  bran  are  assimilable.  If 
this  were  so,  whole  meal  bread  would  be  preferable  to  white 
bread.  I  am  now  engaged  on  experiments  with  the  object  of 
deciding  this  question. 

At  the  Munich  Medical  Congress  Professor  Heubner  ^ 
stated  that  "  15  kilograms  of  meat,^  so  far  as  I  am  aware,  cost 
about  thirty  shillings,  and  that  300  Blaud's  pills  cost  three 
shillings.  I  fear  that  a  large  number  of  people  will  continue 
to  take  the  pills."  I  would,  however,  point  out  that  there  are 
many  cheap  articles  of  food  which  contain  sufficient  iron,  such 
as  potatoes,  carrots,  cabbage.  But  it  is  still  an  open  question 
whether  in  the  equally  cheap  leguminosse,  as  in  the  cereals,  the 
iron  is  not  principally  confined  to  the  husks,  and  whether  the 
iron  in  the  husks  is  assimilable. 

The  danger  of  taking  food  which  is  too  poor  in  iron  is  also 
present  in  children,  who  are  nourished  principally  with  milk 
for  a  long  time  after  lactation  has  ceased.     The  normal  duration 

^Heubner,  loc.  crt.,  p.  174. 

2  1  had  estimated  {loc.  cit.,  p.  144)  that  15  kilos,  meat  contained  0.6  grm. 
Fe,  or  sufficient  to  produce  one-third  of  the  total  hemoglobin  in  a  man. 


IRON  383 

of  suckling  in  human  beings  is  unknown  to  us.  The  instincts 
of  neither  mother  nor  child  give  us  any  clue.  Even  the  habits 
of  aboriginal  races  furnish  us  with  no  data.  Instinct  is  dying 
out,  never  to  return  ;  but  it  is  the  noble  duty  of  science  to 
replace  unerrmg  instinct  by  conscious  knowledge.  If  we  could 
determine  the  time  at  which  the  store  of  iron  possessed  by  the 
infant  at  birth  becomes  used  up  in  the  organs,  the  problem 
would  be  solved.  This  solution  would  be  practicable  if  estima- 
tions were  made  on  the  bodies  of  healthy  children  which  had 
suddenly  met  with  an  accidental  death.  In  the  light  of  our 
present  knowledge  however,  it  seems  probable  that  children 
are  often  rendered  anemic  by  the  milk  diet  being  too  prolonged 
or  too  exclusively  employed ;  and  I  am  pleased  to  hear  that  this 
observation  of  mine  is  confirmed  by  children's  physicians  of 
experience.  For  instance,  Professor  Heubner  stated  at  the 
Munich  Congress  :  ^  "  For  many  years  a  number  of  children's 
physicians  have  recommended  that  a  purely  milk  diet  should 
not  be  continued  too  long  towards  the  end  of  the  suckling 
period.  For  about  ten  years  I  have  myself  adopted  and  have 
also  taught  the  principle  of  giving  other  food  as  a  supplement 
to  milk  after  the  infant  has  reached  the  age  of  9  or  10  months, 
and  this  not  only  in  cases  of  anemia,  but  also  in  other  cachectic 
conditions  of  rickety  children,  although  I  am  not  able  to  adduce 
any  reason  for  this  treatment.  I  may  add  that  I  was  very 
pleased  to  read  the  first  work  published  by  Professor  Bunge  on 
this  subject,  and  have  followed  his  experiments  with  the  greatest 
interest.  Since  then  I  have  found  it  highly  beneficial  to  give 
even  vegetables  to  young  children.  In  my  practice  I  have 
met  with  the  greatest  astonishment  on  the  part  of  parents  who 
consulted  me,  when  I  told  them  to  give  the  child  (which 
perhaps  had  eight  teeth)  a  small  spoonful  of  spinach  or 
cabbage  or  something  of  the  kind  every  day.  This  advice  was 
however  the  result  of  a  long  and  favorable  experience. 
The  advantage  of  this  treatment  must  have  recently  become 
known  in  Berlin.  A  short  time  ago  I  was  somewhat  reproach- 
fully asked  by  the  father  of  an  infant  eight  months  old,  which 
had  not  cut  any  teeth,  why  I  did  not  order  the  child  spinach 
and  apple  sauce.  I  am  quite  sure  that  this  gentleman  had  no 
idea  of  Professor  Bunge's  investigations." 

Dr.  Freund  wrote  to  me  on  April  19,  directly  after  my  com- 
munication at  the  Munich  Congress :  "  I  have  long  since 
observed  and  frequently  state  that  an  exclusive  or  even  pre- 
ponderating milk  diet  for  children  when  they  are  weaned  is  not 
only  insufficient,  but  also  harmful,  in  that  the  children  become 
^  Heubner,  loc.  cit.,  p.  174. 


384  LECTURE    XXV 

pale  and  weak,  and  suffer  from  poorness  of  blood.  The 
children  of  the  lower  classes,  especially  in  the  country,  with 
their  rosy  cheeks,  might  well  be  objects  of  envy  to  many 
mothers  among  the  upper  ten  thousand,  and  I  would  point  out 
that  these  children  partake  of  the  same  food  as  their  parents 
towards  the  end  of  their  first  year  of  life." 

Professor  Monti  ^  of  Vienna  says  in  the  article  he  has  just 
published  on  weaning  and  nutrition  :  "If  children  be  nursed  up 
to  the  twelfth  and  fifteenth  month,  they  do  not  grow  as  they 
should,  even  when  the  milk  is  sufficient  in  quantity.  They  be- 
come anemic,  their  muscles  become  flabby,  and  their  develop- 
ment is  delayed,  so  that,  instead  of  attempting  to  walk  at  the 
end  of  the  first  year,  they  do  not  begin  to  do  so  until  they  are 
about  eighteen  or  nineteen  months  old."  "There  are  certainly 
a  few  races  where  it  is  customary  to  feed  children  at  the  breast 
after  they  have  attained  their  first  year.  We  have  compara- 
tively often  had  the  opportunity  of  seeing  some  of  these  chil- 
dren, which  are  usually  of  Slavonic  parentage,  and  in  all  cases 
the  state  of  nutrition  was  a  bad  one.  Other  food  than  the 
mother's  milk  is  imperatively  indicated."  "The  custom  of 
over-prolonged  nursing  exists  in  France,  in  a  few  parts  of 
Italy,  and,  according  to  hearsay,  in  Japan.  All  authorities  are 
agreed  however  that  the  continuation  of  the  suckling  beyond 
the  proper  time  always  induces  disturbances  in  the  child's  nu- 
trition, and  that  many  cases  of  rickets  must  be  ascribed  to  this 
practice." 

The  other  day  I  came  across  a  very  interesting  and  doubt- 
less unusual  case,  where  an  exclusive  milk  diet  had  been  con- 
tinued into  adult  life.  A  youth  of  eighteen,  from  the  technical 
schools  at  Aarau,  has  lived  on  nothing  but  milk  from  the  time 
of  his  birth.  He  states  that  he  has  occasionally  tried  a  piece  of 
bread  or  a  pear,  but  that  it  had  not  agreed  with  him.  He  has 
an  invincible  dislike  to  all  animal  and  vegetable  food.  His  face 
is  pale,  as  well  as  the  mucous  membrane  of  the  tongue  and  of 
the  conjunctivae.  He  suffers  from  cold  feet  and  hands,  is  easily 
tired  in  walking,  and  has  palpitation  of  the  heart  when  he  goes 
upstairs.  E.  Häusermann  found  that,  although  his  blood  con- 
tained five  million  blood-corpuscles  in  the  cmm.,  it  had  only  8.6 
per  cent,  hemoglobin,  whereas  a  normal  person  has  12—16  per 
cent.  These  are  therefore  conditions  similar  to  those  occurring 
in  cases  of  chlorosis,  viz.,  about  the  usual  number  of  blood-cor- 
puscles, with  a  diminished  amount  of  hemoglobin.^ 

1  Alois  Monti,  "  Ueb.  d.  Entwöhnung,  Ernährung,"  &c.,  Wien.  u.  Leipzig, 
Urban  u.  Schwarzenberg,  p.  104  :   1897. 

2  Häusermann  gives  a  detailed  description  of  this  case,  loc.  cit.,  p.  585. 


IRON  385 

In  order  to  obviate  misimderstaüding,  I  would,  in  conclu- 
sion, lay  stress  upon  the  fact  that  I  do  not  maintain  that  all 
forms  of  anemia,  and  especially  chlorosis,  may  be  cured  by  a 
diet  rich  in  iron.  The  etiology  and  the  nature  of  chlorosis  are 
entirely  obscure,  and  any  treatment  with  iron,  even  if  it  be  only 
the  iron  in  the  food,  is  at  the  best  but  dealing  with  the  symp- 
toms. But  in  anemia,  the  first  thing  to  do  is  to  cease  taking 
food  which  would  make  even  a  healthy  person  bloodless,  and 
afterwards  to  think  of  medicines. 

As  regards  treatment  with  drugs,  I  do  not  deny  the  use  of 
medical  experience  on  the  old  system.  Any  unprejudiced  per- 
son of  good  memory  may  store  up  abundant  statistical  material, 
together  with  the  needful  control  experiments,  without  writing 
down  his  observations  and  communicating  them  to  his  colleagues. 
As  a  matter  of  fact  many  thousands  of  experiences  in  other 
practical  departments,  which  are  likewise  concerned  with  com- 
plex manifestations  of  life,  such  as  farming,  horticulture,  cattle- 
breeding,  hunting,  fishing,  are  collected  in  this  manner,  and 
subsequently  confirmed  by  science.  But  both  in  science  and 
in  practice  it  is  good  to  demand  strict  proofs,  proofs  which  may 
not  only  convince  individuals,  but  may  be  binding  on  all  ex- 
perts as  well  as  on  future  generations. 

I  therefore  venture  to  make  the  following  proposition  with 
regard  to  the  investigation  into  the  action  of  iron.  In  the  first 
place,  cases  of  anemia  as  like  each  other  as  possible  should  be 
sought  out.  Half  of  these  should  be  selected  by  lot  and  be 
treated  with  some  definite  preparation  of  iron,  while  the  other 
half  should  receive  no  iron,  but  in  its  stead  some  indifferent 
medicine,  with  the  assurance  that  this  latter  was  an  unfailing 
remedy.  The  time  should  then  be  determined  at  which  the 
amount  of  hemoglobin  and  the  number  of  blood-corpuscles  had 
risen  by  a  certain  percentage.  Disturbing  factors,  such  as  the 
varying  idiosyncrasies  of  the  different  cases,  can  only  be  eliminated 
by  taking  a  sufficiently  large  number  of  cases  for  the  experiment. 
In  private  practice  we  shall  always  have  to  deal  with  the  diffi- 
culty of  being  able  to  ensure  that  the  medicine  prescribed  is 
really  taken.  I  myself  have  known  of  many  cases  where  the 
doctor  triumphantly  ascribed  the  credit  of  the  chlorotic  patient's 
red  cheeks  to  the  influence  of  the  Blaud  pills,  whereas,  as  a, 
matter  of  fact,  not  a  single  pill  had  been  taken. 


25 


LECTURE   XXVI 


DIABETES    MELLITUS 

In  our  remarks  on  metabolism  in  the  liver,  and  on  the 
source  of  muscular  energy,  we  became  acquainted  with  the  des- 
tiny of  carbohydrates  in  the  body,  and  with  the  way  in  which 
they  are  utilized  under  normal  conditions.  We  are  now  there- 
fore in  a  position  to  consider  the  ijitricate  investigations  con- 
cerning the  destiny  of  carbohydrates  under  pathological  condi- 
tions, and  especially  the  researches  into  the  causes  and  nature  of 
diabetes  mellitus.  This  is  a  subject  with  touches  on  all  branches 
of  physiological  chemistry,  and  about  which  a  complete  library 
of  books  ^  has  been  written,  the  references  to  which  would  alone 
form  a  good-sized  volume. 

These  remarks  will  be  confined  to  the  chronic  form  of 
diabetes.  Transient  glycosuria^  occurs  as  a  consequence,  and 
sometimes  as  an  unimportant  symptom  in  a  great  variety  of 
maladies,  such  as  zymotic  diseases,  digestive  disturbances, 
neuralgia,  cerebral  concussion  and  hemorrhage,  cerebro-spinal 
meningitis,  epilepsy,  psychical  excitement,  poisoning  by  various 
substances,^  &c.  No  satisfactory  explanation  to  account  for  the 
appearance  of  glycosuria  in  all  these  cases  has  yet  been  given, 
and  it  would  lead  us  too  far  to  discuss  all  the  maladies  of  which 
glycosuria  forms  a  symptom. 

But  even  if  we  confined  ourselves  to  that  chronic  disorder 
which  is  strictly  termed  diabetes,  a  complete  account  of  the 
disease  and  its    numerous    and  varying  symptoms  would   be 

1  An  account  of  the  most  important  works  on  diabetes  mellitus  is  given  by 
CI.  Bernard,  "  Le5ons  sur  le  diabete":  Paris,  1877;  Ed.  Kiilz,  "Beiträge  zur 
Pathologie  und  Therapie  des  Diabetes  mellitus "  :  Marburg,  1874  and  1875 ; 
Frerichs,  "  Ueber  d.  Diabetes  "  :  Berlin,  1884.  Frerichs  has  watched  no  less  than 
four  hundred  cases  of  diabetes,  and  has  recorded  the  results  of  his  wide  experi- 
ence in  a  clear,  comprehensive,  and  critical  work,  especially  remarkable  for  its 
objectivity.  We  strongly  recommend  this  book  to  the  student.  Compare  also 
F.  W.  Pavy,  "  On  the  Nature  and  Treatment  of  Diabetes,"  2d  edit.,  London ; 
and  J.  Seegen,  "  Der  Diabetes  mellitus,"  Aufl.  ii. :  Berlin,  1875 ;  and  Arnoldo 
Cantani,  "  Der  Diabetes  mellitus."     Deutsch  von  S.  Hahn  :  Berlin,  1880. 

^  Frerichs  {loc.  cit,,  pp.  25-61)  gives  a  comprehensive  account  of  all  forms  of 
transient  glycosuria. 

^  Of  these  substances,  phloridzin  must  be  particularly  mentioned ;  its 
glycosuric  action  on  animals  containing  no  glycogen  has  been  already  noticed 
(p.  346). 

386 


DIABETES    MELLITUS  387 

oeyond  the  scope  of  the  present  lecture.  It  is  merely  our 
intention  to  collect  the  chief  results  of  the  experimental  investi- 
gations carried  out  for  the  purpose  of  determining  the  causes 
and  nature  of  this  disease. 

Up  to  the  present,  pathological  anatomy  has  led  to  no  con- 
clusion. Post-mortem  examination  of  the  bodies  of  diabetics 
proves  that  there  is  not  a  single  organ  which  does  not  occasion- 
ally show  anatomical  changes  ;  on  the  other  hand,  there  is  not 
a  single  organ  that  does  not  frequently  appear  normal.  It  is 
likewise  impossible,  in  all  cases,  to  decide  whether  these  anato- 
mical changes  are  the  cause  or  the  consequence  of  the  chemical 
changes,^ 

We  will  therefore  restrict  ourselves  to  the  consideration 
of  those  data  which  bear  upon  physiological  chemistry.  The 
most  obvious  symptom,  the  occurrence  of  sugar  in  the  urine, 
has  always  formed  the  basis  of  these  observations. 

As  already  stated,  normal  urine  contains  no  sugar,  or  at 
most  a  trace.  In  diabetes,  often  a  very  considerable  amount 
is  found,  varying  from  a  few  grammes  to  one  kilogramme 
in  twenty-four  hours'  urine.  This  sugar  is  invariably  dextro- 
rotatory grape-sugar.^  With  many  patients  who  have  the 
disease  in  a  mild  form,  the  sugar  disappears  from  the  urine 
if  carbohydrates  are  excluded  from  the  diet ;  with  others  who 
are  more  seriously  affected,  the  excretion  of  sugar  continues, 
even  though  an  exclusive  meat  diet  be  adopted.  In  what  way 
can  we  account  for  the  appearance  of  this  large  amount  of 
sugar  in  the  urine  ? 

Only  two  suppositions  are  open  to  us.  Either  the  kidneys 
have  lost  their  power  of  preventing  the  sugar,  normally  present 
in  the  blood,  from  passing  into  the  urine ;  or  else  the  kidneys 
have  retained  their  usual  function,  but  the  amount  of  sugar  in 
the  blood  has  abnormally  increased. 

The  latter  supposition  must-  be  regarded  as  the  correct 
one  ;  for  the  former  would  imply  that  there  is  less  than  the 
normal  amount  of  sugar  in  the  blood  of  diabetic  patients, 
whereas  the  quantity  found  is,  as  a  matter  of  fact,  always 
above  the  normal.^     The  blood  of  man  and  of  the  dog  normally 

^Frerichs  (loc.  cit.,  pp.  144-183)  gives  a  comprehensive  and  instructive 
tabulated  account  of  the  results  of  fifty-five  autopsies. 

2  J.  Seegen  states  that  he  has  found  levorotatory  sugar  in  the  urine  of  a 
person  suffering  from  'diabetes  intermittens'  {Centralbl.  f.  d.med.  Wissensch.), 
No.  43  :  1884.  Compare  E.  Kiilz,  Zeitschr.  f.  Biolog.,  vol.  xxvii,  p.  228:  1890, 
where  a  critical  summary  will  be  found  of  all  the  statements  relating  to  the 
occurrence  of  levorotatory  sugar  in  urine. 

^  A  diminution  of  the  sugar  in  the  blood  is  found  in  phloridzin  diabetes.  This 
is  therefore  a  different  condition  to  the  '  natural '  diabetes,  and  cannot  be  directly 
applied  to  the  explanation  of  the  latter  condition.    In  phloridzin  diabetes  it  is 


388  LECTURE    XXVI 

contains  from  0.05  to  0.15  per  cent,  of  sugar;  the  blood  of 
diabetic  patients  from  0.22  to  0.44  per  cent.^  If  the  propor- 
tion of  sugar  in  a  dog's  blood  be  artificially  increased  to  more 
than  0.3  per  cent,  by  the  injection  of  a  solution  of  this  sub- 
stance, sugar  passes  through  the  normal  kidneys  into  the  urine. 
No  afPection  of  the  kidneys  has  ever  been  discovered  in  the  first 
stages  of  diabetes. 

It  is  therefore  certain  that  an  abnormal  increase  of  sugar 
in  the  blood  is  the  cause  of  the  appearance  of  sugar  in  the 
urine. 

We  now  come  to  the  question  as  to  the  cause  of  the 
increase  of  sugar  in  the  blood,  and  again  we  have  to  choose 
between  two  explanations.  There  must  be  either  a  larger 
quantity  of  sugar  formed,  or  a  smaller  amount  of  sugar  de- 
composed. 

The  first  explanation  cannot  be  accepted,  for  from  what 
could  the  large  proportion  of  sugar  be  formed?  Not  from 
the  other  carbohydrates,  as  this  would  be  a  normal  process ; 
not  from  the  fats,  as  diabetic  patients  can  digest  and  assimi- 
late them  in  large  quantities.^  As  to  the  proteids,  assuming 
that  a  diabetic  patient  consumed  300  grms.^  in  a  day  (which 
it  would  be  difficult  to  do),  even  this  amount  of  proteid  would 
not  form  more  than  about  200  grms.  of  sugar ;  for  a  large 
proportion  of  the  carbon  must  be  given  off  with  the  nitrogen. 
But  even  if  200  grms.  of  sugar  reached  the  blood  in  the  course 
of  each  day,  it  would  not  cause  diabetes,  so  long  as  the  de- 
composition of  sugar  remained  normal.  A.  man,  on  a  diet  of 
potatoes,  will  form  from  600  to  1000  grms.  of  sugar  per  diem 
from  the  starch  in  his  food,  without  any  sugar  passing  into  the 
urine. 

We  must  therefore  accept  the  other  explanation,  that  the 
increase  of  sugar  in  the  blood  of  diabetic  patients  is  due  to  a 
diminished  sugar  destruction. 

The  power  of  decomposing  sugar  is  never  entirely  arrested ; 


probably  the  kidneys  which  are  primarily  at  fault.  Compare  Minkowski,  Berlin, 
klin.  Wochenschr.,  No.  5:1892;  and  "Untersuch,  üb.  d.  Diabetes  mellitus," 
p.  64 :  Leipzig,  1893. 

'  Carl  Bock  und  Frdr.  Albin  Hofmann,  "  Experimentelle  Studien  über 
Diabetes,"  p.  61 :  Berlin,  1874 ;  Frerichs,  loc.  cit.,  p.  269. 

2  Pettenkofer  and  Voit,  Zeitschr.  f.  Biolog.,  vol.  iii.  pp.  406,  408,  416,  428, 
436  :  1876.  L.  Block  {Deutsch.  Arch.  f.  klin.  Med.,  vol.  xxv.  p.  470 :  1880)  found 
that  only  9  grms.  out  of  from  120  to  150  grms.  of  fat  reappeared  in  the  feces  of 
diabetic  patients. 

'  With  a  diabetic  patient,  the  urea  excreted  in  twenty-four  hours  seldom 
amounts  to  more  than  100  grms.,  which  corresponds  to  300  grms.  of  proteid. 
Pettenkofer  and  Voit  {loc.  cit.,  p.  424)  found  from  46  to  86  grms.  of  urea  in  a 
severe  case  of  diabetes,  the  patient  being  allowed  to  eat  whatever  he  liked. 


DIABETES    MELLITUS  389 

it  is  only  more  or  less  impaired.  Külz  ^  has  shown  that,  even 
in  severe  cases  of  diabetes,  there  is  a  smaller  amount  of  sugar 
in  the  urine  than  would  correspond  to  the  carbohydrates  of  the 
food. 

We  will  now  proceed  to  inquire  how  the  power  of  splitting 
up  sugar  is  impaired  —  a  question  which  again  appears  to  be 
capable  of  but  two  answers.  We  are  only  acquainted  with  two 
processes  by  which  the  food-stuffs  are  destroyed  in  our  tissues : 
decomposition  and  oxidation.  One  of  these  two  processes  must 
be  diminished. 

No  decline  in  the  process  of  oxidation  in  diabetes  has  so  far 
been  proved  from  observations  and  experiments.  The  ultimate 
products  of  proteid  combustion  are  normal,  and  the  fat  appears 
to  be  completely  oxidized  to  carbonic  acid  and  water.  Salts  of 
vegetable  acids  and  lactates  reappear  in  the  urine  as  carbonates.^ 
Benzol  is  oxidized  to  phenol.^  Certain  carbohydrates  even  (such 
as  levulose,  inulin  and  inosit),  and  mannite,  which  is  so  closely 
related  to  the  carbohydrates,  are  decomposed.*  How  is  it  that 
grape-sugar  alone  remains  unoxidized  ? 

That  oxidation  is  not  impeded  is  further  proved  by  the  cir- 
cumstance that  no  increase  of  sugar  in  the  blood,  or  passage  of 
sugar  into  the  urine,^  has  ever  been  observed  either  in  diseases 
connected  with  disturbances  of  external  and  internal  respira- 
tion, or  in  artificial  respiratory  disturbances.® 

We  must  therefore  conclude  that  the  grape-sugar  cannot  be 
oxidized  because  its  decomposition  is  impeded ;  decomposition 
must  precede  oxidation ;  if  the  former  be  impaired,  the  latter 
cannot  take  place,  although  neither  external  nor  internal  res- 
piration is  disturbed. 

O.  Schnitzen^  endeavored  to  support  this  view  by  com- 

'  Kiilz,  "  Beitr.  z.  Path.  u.  Therap.  d.  Diabetes  mellitus,"  pp.  110-119 :  Mar- 
burg, 1874. 

^  O.  Schultzen,  Berliner  klin.  Wochenschr.,  No.  35 :  1872 ;  Nencki  and  Sieber, 
Zeitschr.  f.  prakt.  Chem.,  vol.  xxvi.  p.  34:  1882. 

'"  Nencki  and  Sieber,  loc.  cit.,  p.  36. 

*E.  Kiilz,  "Beitr.  z.  Path.  u.  Therap.  d.  Diabetes  mellitus,"  pp.  127-175: 
Marburg,  1874.  The  experiment  with  mannite  does  not  seem  to  be  convincing, 
because  borborygmi,  flatulence,  and  diarrhea  occurred  after  taking  it.  It  is  pos- 
sible that  the  mannite  introduced  was  mostly  decomposed  by  fermentative  organ- 
isms in  the  alimentary  canal.  A  small  amount  was  found  unaltered  in  the  urine. 
With  respect  to  inosit,  vide  also  E.  Kiilz,  Sitzungsber.  d.  Ges.  z.  Beförderung  d. 
ges.  Naturw.  zu  Marburg,  No.  4:  1876. 

5  Von  Mering,  Arch.  f.  Physiol.,  p.  381 :  1877. 

^  Senator,  Virchow's  Arch.,  vol.  xlii.  p.  1 :  1868. 

■^  O.  Schultzen,  loc.  cit.  The  view  that  sugar  could  only  be  oxidized  sub- 
sequently to  decomposition  was  first  suggested  by  Scheremetjewski  in  a  research 
published  from  C.  Ludwig's  laboratory  {Arb.  au-s  d.physiol.  Anstalt  zu  Leipzig, 
p.  145:  Jahrg.  1868;  Leipzig,  1869).  Compare  also  Nencki  and  Sieber,  loc.  cit., 
p.  39. 


390  LECTUEE    XXVI 

paring  observations  on  diabetics  with  those  on  persons  suffering 
from  phosphorus-poisoning.  As  we  have  already  seen  (p.  363), 
oxidation  is  diminished  in  cases  of  phosphorus-poisoning. 
Instead  of  sugar,  lactic  acid  occurs  in  the  urine ;  and  this 
Schnitzen  regarded  as  a  normal  product  of  the  decomposition 
of  grape-sugar.  He  therefore  said  that,  after  phosphorus- 
poisoning,  the  power  of  oxidation  was  lost,  but  not  that  of 
decomposition,  while  the  reverse  was  the  case  in  diabetes. 
Hence,  after  phosphorus-poisoning,  the  normal  product  of  de- 
composition appears  in  the  urine,  while  in  diabetics,  in  spite  of 
undisturbed  oxidation,  the  unaltered  grape-sugar  appears  in  the 
urine. 

The  following  experiment  of  Pettenkofer  and  Voit^  may 
be  interpreted  in  the  same  way.  By  means  of  their  respiratory 
apparatus,  they  showed  that  a  diabetic  took  in  less  oxygen  and 
excreted  less  carbonic  acid  than  a  healthy  person. 

It  was  not  that  less  sugar  was  broken  up  because  the  in- 
come of  oxygen  was  reduced,  but  that  less  oxygen  was  used  up 
because  the  formation  of  oxidizable  products  of  decomposition 
was  diminished. 

This  theory  is  very  inviting,  but  objections  may  be  raised 
to  it.  The  fact,  already  mentioned  in  our  remarks  concern- 
ing internal  respiration  (p.  259),  that  certain  substances, 
after  introduction  into  the  body,  appear  in  the  urine  con- 
jugated with  glycuronic  acid,  is  opposed  to  the  view  that 
decomposition  must  precede  oxidation.  Glycuronic  acid  is 
undoubtedly  a  product  of  oxidation,  but  not  of  decomposition  ; 
all  six  atoms  of  carbon  are  still  united,  and  yet  oxidation  has 
begun.  Conjugation  alone  prevents  its  completion ;  and  as 
soon  as  the  compound  is  split  up,  nothing  can  stop  its  further 
progress. 

Nencki  and  Sieber  say,  "  We  do  not  doubt  that,  if  the 
diabetic  could  break  up  sugar  to  form  lactic  acid,  he  would 
afterwards  be  able  completely  to  oxidize  the  sugar."  ^  But 
lactic  acid  is  evidently  not  the  normal  product  of  decompo- 
sition of  sugar  in  the  body.  The  sarcolactic  acid,  which  is 
invariably  present  in  the  organs,  probably  arises  from  proteid 
(p.  312).  As  nothing  is  yet  known  concerning  the  course 
and  sequence  of  the  decomposition  and  oxidation  of  sugar  in 
the  organism  under  normal  conditions,  we  are  scarcely  in  a 
position  to  inquire  into  the  abnormal  chemical  processes  occur- 
ring in  diabetes. 

'  Pettenkofer  and  Voit,  Zeitschr.  f.  Biolog.,  vol.  iii.  pp.  428,  429,  431,  and 
432 :  1867. 

^  Nencki  and  Sieber,  Journ.  f.  prakt.  Chem.,  vol.  xxvi.  p.  37 :  1882. 


DIABETES    MELLITUS  391 

Attention  must  be  particularly  called  to  the  occurrence  in 
the  diabetic  urine  of  substances  which  are  evidently  products  of 
incomplete  oxidation  :  oxybutyric  acid,  aceto-acetic  acid,  and 
aceton.  ^  They  probably  arise  from  the  proteids,  for  their 
amount  is  independent  of  any  addition  of  carbohydrates  to  the 
diet,  but  increases  with  increased  proteid  metabolism.^  They 
do  not  occur  in  all  cases  of  diabetes,  but  generally  in  the  more 
severe  forms  of  the  disease,  in  which  the  destructive  metabolism 
of  proteid  is  augmented. 

The  oxybutyric  acid  in  diabetic  urine  is  the  levorotatory 
/3-oxybutyric acid (CH3-CH(OH)-CH2-COOH).  TheacetJ- 
acetic  acid  (CH3— CO— CH2— COOH),  which  can  be  artificially 
produced  by  oxidation  from  /?-oxybutyric  acid,  breaks  up  readily 
into  aceton  and  carbonic  acid  :  CH3  —  CO  —  CHg  —  COOH  = 
CH,  —  CO  —  CH3  +  COg.  The  aceto-acetic  acid  and  the  aceton 
in  diabetic  urine  have  probably  originated  in  the  same  way  in 
the  organism. 

In  the  last  stage  of  diabetes,  when  coma  sets  in,  the  amount 
of  oxybutyric  acid  increases,  while  that  of  aceton  diminishes.  ^ 
This  fact  also  appears  to  argue  in  favor  of  an  increasing  decline 
in  the  power  of  oxidation. 

It  must  however  be  noted  that  the  occurrence  of  oxybutyric 
acid,  aceto-acetic  acid,  and  aceton  is  not  confined  to  diabetes, 
but  has  been  observed  in  many  other  maladies.^  These  anom- 
alous products  of  metabolism  may  possibly  be  a  direct  conse- 
quence, not  of  diabetes  itself,  but  of  certain  complications  which 
frequently  accompany  the  disease. 

On  the  other  hand,  it  must  be  remembered  that  wasting  of 
the  tissues  and  general  cachexia,  in  short,  increased  destruction 
of  the  nitrogenous  constituents  of  the  body,  invariably  take 
place  in  all  the  diseases  in  which  acetonuria  has  been  observed, 
such  as  febrile  infectious  diseases,  carcinoma,  mental  affections 

^  Stadelmann,  Arch.  /.  exper.  Path.  u.  Pharm.,  toI.  xvii.  p.  419:  1883  ;  and 
Zeitschr.  f.  Biolog.,  vol.  xxi.  p.  140:  1885;  Minkowski,  Arch.  f.  exper.  Path.  u. 
Pharm.,  vol.  xviii.  pp.  35,  147:  1884;  E.  Kiilz,  Zeitschr.  f.  Biolog.,  vol.  xx.  p. 
165  :  1884 ;  and  vol.  xxiii.  p.  329  :  1886 ;  and  Arch.  f.  exper.  Path.  ii.  Pharm.,  vol. 
xviii.  p.  291 :  1884 ;  End.  von  Jaksch,  "  Ueber  Acetonurie  u.  Diaceturie  "  :  Berlin, 
1885 ;  H.  Wolpe,  Arch.  f.  exper.  Path.  u.  Pharm. ,yoI.  xxi.  p.  138 :  1886 ;  Frerichs, 
loc.  cit.,  pp.  114-118. 

^G.  Rosenfeld,  Deutsch,  med.  Wochenschr.,  No.  40:  1855;  Wolpe,  loc.  cit., 
pp.  150-155.  The  older  literature  is  here  quoted.  Also  M.  J.  Rossbaeh,  Corre- 
spondensblatt  des  allgem.  ärztlichen  Vereins  für  Thüringen,  No.  3  :  1887 ;  Chem. 
Centralbl.  p.  1437  :  1887. 

^  Wolpe,  "  Unters,  ü.  d.  Oxybuttersäure  des  diabetischen  Harnes,"  Dissert.: 
Königsberg,  1886  ;  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxi.  p.  157  :  1886. 

^R.  von  Jaksch,  "Ueber  Acetonurie  u.  .Diaceturie,"  pp.  54-91:  Berlin, 
1885 ;  Külz,  Zeitschr.  f.  Biolog.,  vol.  xxiii.  p.  329 :  1886;  A.  Baginsky,  Du  Bois' 
Arch.,  p.  349  :  1887. 


392  LECTURE    XXVI 

accompanied  by  inanition,  &c.  The  occurrence  of  aceto-acetic 
acid  has  likewise  been  noticed  in  the  urine  of  healthy  persons 
after  prolonged  fasting.^  Increased  decomposition  of  proteid 
now  appears  to  be  an  accompaniment  of  diabetes  also  :  at  least, 
it  was  proved,  by  careful  experiment  in  three  severe  cases,  that 
the  patient  excreted  more  nitrogen  than  a  healthy  person  on 
exactly  the  same  diet.  The  first  investigation  of  the  kind  was 
carried  out  by  Gaehtgens  ^  in  his  clinique  at  Dorpat,  the  second 
by  Pettenkofer  and  Voit,  ^  and  the  third  by  Frerichs.* 

These  experiments  might  be  taken  to  mean  that  the  increased 
decomposition  of  proteids  in  diabetes  was  a  consequence  of  the 
inadequate  breaking  up  of  the  sugar  ;  that,  because  the  chemical 
potential  energy  of  the  sugar  was  not  completely  utilized,  the 
proteid  must  assist  in  furnishing  the  kinetic  energy  necessary 
for  the  performance  of  the  functions  of  the  body.  This  would 
be  analogous  to  the  behavior  of  normal  muscle,  which,  as  we 
have  seen,  has  recourse  to  its  store  of  proteid  as  soon  as  the 
supply  of  non-nitrogenous  food  runs  short.  But  this  is  only  a 
teleological,  not  a  physico-chemical  explanation,  and  gives  no 
account  of  the  causal  connection.  We  must  concede  the  pos- 
sibility that  the  increased  decomposition  of  proteid  may  be  the 
first  sign  of  disturbance  in  the  metabolism  of  the  organs,  and 
may  usher  in  the  wasting  of  the  tissues  and  all  the  other 
troubles.  It  may  be  also  that  the  occurrence  of  oxybutyric 
acid,  aceto-acetic  acid,  and  aceton  in  diabetes  is  not  due  to  the 
reduced  supply  of  oxygen,  any  more  than  it  is  in  the  case 
of  the  other  diseases  mentioned.  The  tissues  may  receive  their 
normal  supply  of  oxygen,  but  the  products  of  decomposition 
may  have  risen  above  the  normal  amount ;  and  that  part  of 
them  which  reaches  the  blood  in  a  state  of  incomplete  oxi- 
dation, cannot  be  further  oxidized  there  because,  as  we  have 
already  seen  (p.  247),  no  processes  of  oxidation  take  place  in 
the  blood. 

The  power  possessed  by  a  diabetic  of  utilizing  levorotatory 
sugar  is  a  remarkable  fact,   which  was  observed   by  Kiilz.^ 

^  See  the  interesting  notice  in  the  report  of  the  investigations  carried  out  on 
the  'professional  faster,'  Cetti,  in  Berlin  {Berliner  Wochenschrift,  vol.  xxiv.  p. 
434:1887). 

^Carl  Gaehtgens,  "  Ueber  den  Stoffwechsel  eines  Diabetikers,  verglichen 
mit  dem  eines  Gesunden,"  Dissert.:  Dorpat,  1886. 

3  Pettenkofer  and  Voit,  Zeitschr.  f.  Biolog.,  vol.  iii.  pp.  400,  408,  412-414, 
425.     An  account  of  the  older  literature  will  be  found  here,  pp.  425-426. 

*  Frerichs,  loc.  cit.,  p.  276,  et  seq. 

5  Külz,  loc.  cit.,  pp.  130-167.  Also  Worm-Müller,  Pfliiger's  Arch.,  vol. 
xxxiv.  p.  576:  1884;  S.  de  Jong,  "  Overomzetting  van  milksuiker  by  diabetes 
mellitus,"  Dissert.:  Amsterdam,  1886 ;  and  Franz  Hofmeister,  Arch.  f.  exper.  Path, 
u.  Pharm.,  vol.  xxv.  p.  240:  1889. 


DIABETES    MELLITUS  393 

He  showed  that  after  eating  100  grms.  of  levorotatoiy  fruit- 
sugar,  no  sugar  appeared  in  the  urine  of  a  patient  who  was 
but  slightly  affected  with  the  disease,  and  that  the  amount 
of  sugar,  which  consisted  only  of  dextrorotatory  grape-sugar, 
was  not  increased  in  the  urine  of  a  patient  who  had  a  severe 
form  of  diabetes. 

Inulin  behaves  in  the  same  manner  as  levulose.  It  is 
found  in  the  roots  of  elecampane,  chicory,  and  dandelion,  and 
in  the  tubers  of  dahlias,  where  it  plays  the  same  part  as  the 
starch  in  the  potato  tubers.  Inulin  stands  in  the  same  rela- 
tion to  levulose  as  starch  does  to  dextrose :  on  boiling  with 
dilute  acid,  it  is  split  up  with  hydration  to  form  levulose,  just 
as  starch  is  changed  into  dextrose.  Inulin  evidently  under- 
goes this  decomposition  in  the  organism  as  well ;  like  levulose, 
it  is  consumed  in  the  body  of  a  diabetic. 

It  is  M'ell  known  that,  on  boiling  with  acids  as  well  as 
by  the  action  of  ferments,  cane-sugar  is  split  up  into  equal 
quantities  of  levulose  and  dextrose.  In  conformity  with  this, 
Kiilz  observed  that,  after  the  administration  of  cane-sugar  in 
the  aggravated  form  of  diabetes,  the  increase  in  the  excretion 
of  dextrose  was  equal  to  half  the  amount  of  the  cane-sugar 
eaten.  These  experiments  of  Kiilz  on  the  fate  of  levorotatory 
sugar  in  diabetics  have  since  been  repeated  many  times.^ 
The  results  are  however  contradictory,  and  it  appears  that 
different  patients  vary  in  their  power  of  utilizing  this  sugar. 
In  general,  the  statement  that  levorotatory  sugar  is  entirely 
or  in  greater  part  assimilated  has  been  confirmed.  In  many 
cases,  however,  a  small  quantity  of  dextrorotatory  sugar 
appeared  in  the  urine  as  a  result  of  the  ingestion  of  levo- 
rotatory ;  and  the  question  has  still  to  be  decided  whether  in 
such  cases  the  levorotatory  sugar  has  been  directly  converted 
into  dextrorotatory,  or  whether  it  has  merely  exercised  in 
the  body  a  sparing  influence  on  the  latter. 

This  limitation  of  the  power  in  diabetics  to  utilize  levo- 
rotatory sugar  only  is  no  isolated  phenomenon  in  animate 
nature.  Certain  fungi  and  bacteria  act  in  the  same  way  as  the 
cells.^    Of  the  optically  inactive  lactic  acid,  which  contains  equal 

^  J.B.B.&Tcr&tt,  Zeitschr.  f.  physiol.  Chem.,  vol.  xix.  p.  137:  1884;  P. 
Palma,  Zeitschr.  /.  Heilk.,  vol.  xv.:  1894;  W.  Hale  White,  Zeitschr.  f.  Hin. 
3fed.,  vol.  xxvi.  p.  332:  1894;  Karl  Grube,  ibid.,  vol.  xxvi.  p.  340:  1894; 
C.  A.  Socin,  "  Wie  verhalten  sich  Diabetiker  Lävulose-Milchzuckerzufuhr 
gegenüber?"  Dissert.:  Strassburg,  1894.    The  earlier  literature  is  here  given. 

2  Pasteur,  Compt.  rend.,  vol.  xlvi.  p.  615  :  1858 ;  vol.  li.  p.  298 :  1860 ; 
vol.  Ivi.  p.  416  :  1863;  J.  A.  Le  Bel,  ibid.,  vol.  Ixxxvii.  p.  213:  1878  ;  vol. 
Ixxxix.  p.  312  :  1879 ;  vol.  xcii.  p.  843  :  1881 ;  J.  Lewkowitsch,  Ber.  d.  deutsch. 
Chem.  Ges.,  vol.  xv.  p.  1505 :  1882  ;  vol.  xvi.  pp.  1569,  2720,  2722 :  1883.    Also 


394  LECTURE    XXVI 

quantities  of  dextrorotatory  and  levorotatory  lactic  acid,  the 
Fenicillium  glaucum  consumes  the  latter  only,  leaving  the 
former  untouched ;  in  the  same  way,  this  fungus  leaves  the 
dextrorotatory  only  in  a  mixture  of  both  kinds  of  mandelic 
acid.  Saccharomyces  ellipsoideus,  on  the  contrary,  consumes 
the  dextrorotatory  mandelic  acid  only,  leaving  the  levorota- 
tory ;  and  this  is  also  the  case  with  a  certain  variety  of  bac- 
terium. PenieiUium  glaucum  behaves  in  the  opposite  way 
towards  tartaric  and  glyceric  acids  compared  with  its  action  on 
lactic  and  mandelic  acids ;  it  leaves  the  levorotatory  tartaric 
and  glyceric  acids  untouched. 

From  the  above  remarks,  it  appears  that  so  far  we  have 
only  definitely  ascertained  that  the  power  of  utilizing  dextro- 
rotatory sugar  is  diminished  in  diabetes. 

Now,  as  the  bulk  of  the  sugar  is  normally  decomposed  in 
the  muscles,  it  seems  probable  that  diabetes  may  fundamentally 
be  due  to  a  disturbance  of  the  chemical  processes  in  muscle. 

Insufficient  use  of  the  muscles,  a  sedentary  mode  of  life, 
are  frequently  given  as  causes  of  diabetes.  This  harmonizes 
with  the  fact  that  the  disease  comparatively  often  (30  per 
cent,  of  all  cases)  occurs  in  stout  people.  Obesity  is  invari- 
ably a  result  of  insufficient  muscular  exertion  (see  end  of 
Lecture  XXIV.).  Moveover,  a  few  cases  of  diabetes  have 
been  successfully  treated  by  systematic  muscular  exercise.^ 

But  the  chemical  processes  in  muscle  are  subject  to  the 
influence  of  the  nervous  system,  and  numerous  observations 
tend  to  show  that  the  symptoms  in  diabetes  are  caused  by 
disturbances  which  originate  in  the  central  nervous  system. 
The  disease  sometimes  occurs  immediately  after  and  may  be 
traced  to,  injury  to  the  head,  or  it  accompanies  organic  affec- 
tions of  the  brain  (hemorrhages,  tumors,  sclerosis),  or  other 
nervous  diseases,  psychoses,  &c.  Occasionally  violent  mental 
excitement  or  neuralgia  has  caused  an  outbreak  of  the 
malady.  In  post-mortem  examinations  of  diabetics,  the  brain 
more  frequently  shows  pathological  changes  than  any  other 
organ. 

Seegen,^  who  has  treated  over  a  thousand  cases  of  diabetes, 
declares  that  90  out  of  every  100  of  such  cases  suffer  from  some 
form  of  nervous  disorder,  and  adds  that,  in  the  numerous  cases 
of  hereditary  diabetes  in  one  and  the  same  family,  some  may 
suffer  from  some  form  of  psychical    disorder,  in  most   cases 

Em.  Bourquelot,  Compt.  rend.,  vol.  c.  pp.  1404,1466;  vol.  ci.  pp.  68,  958:  1885  ; 
Maumene,  ibid.,  vol.  c.  p.  1505 ;  vol.  ci.  p.  695  :  1885 ;  H.  Leplay,  vol.  ci. 
p.  479  :  1885. 

1  Külz,  loc.  cit.,  vol.  i.  pp.  179-216;  and  vol.  ii.  pp.  177-180. 

2  J.  Seegen,  "  Die  Zuckerbildung  im  Thierkörper,  &c.,"  p.  263 :  Berlin,  1890. 


DIABETES    MELLITUS  395 

melancholia,  leading  off  into  suicide,  while  other  members  are 
diabetic. 

Much  confusion  has  arisen  owing  to  the  endeavor  to  ex- 
plain the  nature  of  chronic  or  '  natural '  diabetes  (as  it  has 
been  called),  from  the  observations  carried  out  on  '  artificial ' 
diabetes.  CI.  Bernard  has  shown  that  a  puncture  in  the  floor 
of  the  fourth  ventricle,  midway  between  the  origins  of  the 
auditory  and  pneumogastric  nerves,  is  followed  by  the  passage 
of  sugar  into  the  urine.  This  artificial  diabetes  is  obviously 
quite  a  different  process  to  the  natural  disease.  It  lasts  only 
for  a  few  hours ;  and  if,  at  the  expiration  of  this  time,  when 
the  urine  has  again  become  free  from  sugar,  the  animal  be 
killed,  no  glycogen  will  be  found  in  the  liver.  If  all  glycogen 
be  removed  from  a  dog  by  starvation,  puncture  of  the  '  diabetic 
center'  remains  without  effect.^ 

If  a  solution  of  grape-sugar  be  injected  into  the  mesenteric 
vein  of  a  healthy  dog,  which  has  been  deprived  of  glycogen  by 
starvation,  very  little  sugar  appears  in  the  urine.  But  if  the 
liver  be  freed  from  glycogen  by  puncture  of  the  floor  of  the 
fourth  ventricle,  and  the  injection  into  the  mesenteric  vein 
be  then  given,  a  very  large  amount  of  sugar  is  found  in  the 
urine.^ 

Artificial  diabetes  therefore  is  due  to  the  inability  of  the 
liver,  in  consequence  of  disturbed  innervation,  to  retain  the 
glycogen.  The  blood  becomes  flooded  with  sugar,  which  passes 
into  the  urine. 

If  natural  diabetes  were  due  to  the  same  cause,  and  if  the 
liver  had  lost  its  power  of  regulating  the  amount  of  sugar  in 
the  blood,  of  storing  carbohydrates  during  absorption,  and  of 
supplying  sugar  to  the  blood  according  to  the  needs  of  the 
economy,  we  should  expect  to  find  that  the  amount  of  sugar 
in  the  blood  of  diabetics  would  sometimes  be  above  and  some- 
times below  normal.  This  is  not  the  case  ;  it  has  always  been 
found  to  be  increased. 

The  objection  may  be  raised  that  the  diabetic  patient 
takes  food  in  such  quantities  and  so  often,  that  absorption 
is  never  interrupted,  and  that  the  blood  is  constantly  loaded 
with  sugar. 

We  must  therefore  try  to  decide  the  question  in  a  direct 

^  Leopold  Seelig,  "  Vergleichende  Untersuchungen  über  den  Zuckerverbrauch 
im  diabetischen  und  nicht  diabetischen  Thiere,"  Dissert.:  Königsberg,  1873. 
The  works  of  Pavy  and  Dock  are  quoted  here.  Luchsinger  has  published  a  con- 
firmation of  these  results :  "  Exper.  u.  krit.  Beiträge  zur  Physiol,  u.  Pathol,  des 
Glycogens,"  Dissert.,  p.  72:  Zürich,  1875. 

^Naunyn,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  iii.  p.  98:  1875.  A  critical 
account  is  here  given  of  the  earlier  works  on  this  point. 


396  LECTURE    XXVI 

manner,  and  ascertain  whether  a  diabetic  liver  contains  gly- 
cogen.    This  method  has  actually  been  adopted. 

Külz^  examined  the  liver  of  a  patient  who  suffered  from 
the  aggravated  form  of  diabetes,  and  had  been  for  a  long  time 
before  his  death  restricted  to  a  diet  of  meat.  The  patient 
had  taken  his  last  meal  thirty-four  hours  before  death,  and 
had  been  moribund  for  twenty-eight  hours.  The  post-mortem 
took  place  twelve  hours  after  death.  About  the  tenth  part 
of  the  liver  served  for  the  determination  of  glycogen,  and 
yielded  roughly  0.7  grm.  of  glycogen.  Külz  estimated  the 
amount  of  glycogen  in  the  whole  liver  at  from  10  to  15  grms. 
Besides  this,  it  contained  a  large  quantity  of  sugar,  part  of 
which  also  originated  from  the  glycogen.^  The  amount  of  gly- 
cogen during  life  must  therefore  have  been  very  considerable. 

Von  Mering^  had  the  opportunity  of  examining  the  livers 
of  four  diabetics  in  Frerichs'  wards.  "  Two  of  them,  who  died 
of  phthisis,  and  who  had  no  sugar  in  the  urine  eighteen  and 
twenty  hours  before  decease  (although  there  had  previously 
been  a  considerable  amount),  exhibited  neither  glycogen  nor 
sugar  in  their  livers,  although  in  one  case  the  post-mortem 
examination  took  place  immediately  after  death.  In  the  two 
other  cases  where  the  diabetics  died  suddenly,  and  the  urine 
removed  from  the  bladder  after  death  was  full  of  sugar,  both 
glycogen  and  sugar  were  found  in  abundance." 

M.  Abeles*  examined  the  organs  in  the  bodies  of  five 
diabetics,  in  E.  Ludwig's  laboratory  in  Vienna.  No  glycogen 
was  found  in  any  of  the  organs  examined  in  two  cases,  one  of 
which  had  died  of  phthisis,  and  the  other  of  prolonged  furun- 
culosis  and  metastatic  purulent  pericarditis.  The  remaining 
patients  had  died  from  diabetic  coma.  The  organs  were  not 
examined  for  several  hours  after  death.  The  liver  was  ex- 
amined in  two  cases,  and  a  little  glycogen  was  found  :  0.16 
grm.  and  0.59  grm.     There  was  none  of  the  muscles. 

The  liver  of  living  diabetics  has  also  been  examined  for 
glycogen  in  Frerichs'  wards.^  These  experiments  are  so  im- 
portant that  I  will  quote  the  passages,  unfortunately  very  short, 
in  which  they  are  described. 

'  Külz,  Pflüger's  Arch.,  vol.  xiii.  p.  267  :  1876.  See  also  the  older  statemeata 
of  Kühne,  Virchow's  Arch.,  vol.  xxxii.  p.  543:  1865;  and  M.  Jaffe,  ibid.,  vol. 
xxxvi.  p.  20  :  1866. 

^  To  obtain  an  exact  estimate  of  the  glycogen,  the  liver  must  be  immersed  in 
boiling  water  directly  after  death,  in  order  to  stop  the  fermentative  action  by 
which  the  glycogen  would  otherwise  be  broken  up. 

■^  Von  Mering,  Pflüger's  Arch.,  vol.  xiv.  p.  284:  1877. 

*  M.  Abeles,  Centralbl.  f.  d.  med.  Wissensch.,  p.  449:  1885. 

^  Frerichs,  loc.  cit.,  p.  272.  Also  plates  of  the  histological  sections  of  the 
livers. 


DIABETES    MELLITUS  397 

"  Professor  Ehrlich  eiFected  it  by  means  of  a  fine  trocar, 
which  had  been  carefully  disinfected,  and  which  was  inserted 
in  the  parenchyma  of  the  liver.  When  the  instrument  was 
removed,  sometimes  a  little  blood  only,  but  generally  a  few 
hepatic  cells,  either  isolated  or  united  m  groups,  were  found  in 
the  tube ;  there  was  occasionally  a  somewhat  larger  piece  of  the 
liver,  which  was  hardened  in  alcohol,  and  cut,  after  being  im- 
bedded in  celloidon.  In  this  way,  we  were  able  to  examine  the 
hepatic  tissue  during  life  in  three  cases.  They  had  all,  both 
healthy  and  diabetic,  eaten  heartily,  especially  of  amylaceous 
food.  The  puncture  was  made  from  four  and  a  half  to  five  and 
a  half  hours  after  the  meal. 

"  A  considerable  quantity  of  glycogen  was  found  in  the 
first  case,  that  of  a  healthy  man,  addicted  however  to 
alcohol.  The  cells  in  the  peripheral  regions  of  the  acini 
had  undergone  fatty  degeneration,  but  contained  glycogen 
as  well. 

"  The  second  case  was  that  of  the  diabetic  Dn.  The  hepatic 
cells  were  almost  free  from  glycogen,  though  a  few  showed  a 
slightly  brownish  hue,  denoting  the  presence  of  traces  of  this 
substance. 

"  In  the  third  case,  that  of  a  diabetic  woman,  a  tolerably 
large  amount  of  glycogen  was  found  in  the  hepatic  cells.  The 
distribution  of  glycogen  was  very  unequal,  parts  containing  but 
little  alternating  with  others  richly  provided  with  it.  Large 
granules  of  glycogen,  which  frequently  filled  almost  the  whole 
of  the  cells,  were  often  found  at  the  margin  of  the  lobule. 
They  did  not  however  consist  of  pure  glycogen,  but  mainly  of 
a  supporting  subtance,  as  their  yellowish  color  denoted.  They 
could  not  be  regarded  as  artificial  products  caused  by  the  alcohol, 
as  they  occurred  likewise  in  dried  preparations.  The  nuclei 
were  generally  free  from  glycogen,  although  in  one  place  gly- 
cogen appeared  to  be  deposited  round  the  nucleolus.  This  is 
very  analogous  to  the  deposits  of  starch  round  the  nucleoli  in 
plants. 

"  Examination  of  the  dried  preparations,  which  were  ob- 
tained from  repeated  punctures,  showed  the  same  result, 
i.  e.,  absence  of  glycogen  in  case  2,  and  a  moderate  amount 
in  case  3." 

I  think  these  facts  also  indicate  that  we  cannot  apply  the 
term  diabetes  to  one  single  malady  ;  lesions  similar  to  those 
which  produce  artificial  diabetes,  may  also  produce  certain 
forms  of  the  malady  (and  especially  glycosuria  from  injury 
to  the  medulla  oblongata),  but  by  no  means  all. 

The  fact  that  no  sugar  passes  into  the  urine  in  cases  of 


398  LECTÜEE    XXVI 

extensive  hepatic  disease,  in  cirrhosis  of  the  liver,  and  in  phos- 
phorus-poisoning, is  very  remarkable.  Frerichs  could  not 
detect  any  sugar  in  the  urine,  even  after  large  quantities  of 
grape-sugar  had  been  taken,  in  cases  of  cirrhosis  of  the  liver, 
where  a  subsequent  autopsy  showed  complete  degeneration  of 
that  organ.^  After  administration  of  from  100  to  200  grms.  of 
grape-sugar  to  patients  suffering  from  phosphorus-poisoning  in 
Frerichs'  wards  a  small  amount  of  it  was  traced  in  the  urine 
in  two  cases,  while  in  seventeen  others  the  result  was  negative. 
No  trace  of  sugar  or  glycogen  was  ever  found  in  the  liver  in 
any  case  of  phosphorus-poisoning,  where  fatty  degeneration  of 
that  organ  had  set  iu.^ 

Diabetes  is  evidently  not  due  only  to  a  disturbance  of  the 
glycogenic  function  of  the  liver.  As  far  as  I  know,  the  muscle 
of  diabetics  has  only  been  examined  for  glycogen  in  two  cases, 
and,  as  already  stated,  with  a  negative  result.^ 

Although  the  artificial  diabetes  discovered  by  Bernard  does 
not  serve  to  explain  the  natural  form  of  this  disorder,  another 
kind  of  artificial  diabetes,  which  has  been  the  subject  of  much 
research  during  the  last  few  years,  seems  to  bring  us  nearer  to 
a  solution  of  the  problem — I  mean  the  diabetes  that  follows  the 
extirpation  of  the  pancreas. 

It  was  long  ago  pointed  out  that  pathological  alterations  in 
the  pancreas  are  frequently  to  be  found  in  autopsies  on  diabetics. 
Frerichs*  especially  drew  attention  to  this  point,  and  showed 
that,  in  fifty-five  fatal  cases  of  diabetes,  well-marked  macro- 
scopic changes  in  the  pancreas  were  to  be  found  in  eleven  of 
them.  The  experimental  proof  of  the  connection  of  the  pan- 
creas with  diabetes  could  however  only  be  given  later,  after 
surgical  technique  and  especially  the  aseptic  method  had 
reached  the  state  of  perfection  necessary  for  so  serious  an 
operation. 

J.  von  Mering  and  O.  Minkowski^  have  operated  on  more 
than  fifty  dogs,  and  have  found  that,  in  all  cases  without  excep- 
tion where  the  complete  extirpation  of  the  pancreas  had  been 
successfully  carried  out  and  the  animals  had  survived  more  than 
twenty-four  hours,  well-marked  and  severe  diabetes  was  pro- 
duced with  all  its  characteristic  symptoms,  such  as  great  thirst, 
large  appetite,  polyuria,  and  rapid  decline  of  strength. 

^  Frerichs,  loc.  cit.,  p.  43.  ^  Ibid.,  p.  45. 

'  Abeles,  loc.  cit. 

*  Frerichs,  loc.  cit.,  pp.  144-183.    See  also  the  case-histories,  pp.  238-248. 

^  J.  von  Mering  and  O.  Minkowski,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol. 
xxvi.  p.  371:  1890.  Minkowski,  Berl.  klin.  Wochenschr.,  No.  .5:  1892;  and 
"  Untersuch,  üb.  d.  Diabetes  mellitus  nach  Exs.  d.  Pankreas,"  Leipzig,  1893.  In 
this  latter  work  the  rest  of  the  literature  ou  the  subject  is  fairly  fully  given. 


DIABETES    MELLITUS  399 

The  excretion  of  sugar  began  in  some  cases  four  to  six 
hours  after  the  operation,  in  most  cases  somewhat  later,  often 
not  until  the  next  day.  Within  twenty-four  to  forty-eight 
hours,  the  glycosuria  reached  its  highest  point,  the  sugar 
amounting  to  between  5  and  11  per  cent,  of  the  urine,  even 
before  the  animals  had  taken  any  food  whatsoever.  Even  after 
seven  days'  starvation  or  exclusive  meat  diet,  the  sugar  did  not 
disappear  from  the  urine.  For  instance  in  one  dog  weighing 
8  kilos,  on  a  plentiful  diet  of  meat  and  bread,  the  daily  excre- 
tion of  sugar  over  a  considerable  time  amounted  to  between  70 
and  80  grms.  In  some  cases  large  quantities  of  aceton,  aceto- 
acetic  acid,  and  oxybutyric  acid  also  made  their  appearance  in 
the  urine.  The  sugar  was  also  largely  increased  in  the  blood. 
In  one  case,  on  the  sixth  day  after  the  operation,  it  amounted 
to  0.3  per  cent. ;  in  another  case,  on  the  twenty-seventh  day, 
to  0.46  per  cent. 

The  glycogen,  all  but  minute  traces,  disappeared  early  from 
the  organs.  Dextrorotatory  grape-sugar,  administered  with  the 
food,  reappeared  without  loss  in  the  urine.  Levorotatory 
sugar  was  in  great  part  utilized,  though  a  certain  proportion 
was  converted  into  dextrorotatory,  and  excreted  by  the  kid- 
neys.^ On  feeding  with  levorotatory  sugar,  glycogen  was  de- 
posited in  the  liver  and  muscles. 

These  statements  of  Mering  and  Minkowski  have  been  con- 
firmed by  many  other  authors,  especially  by  Lupine  ^  and 
H^don.^ 

If  we  now  attempt  to  explain  the  connection  between  the 
extirpation  of  the  pancreas  and  diabetes,  the  idea  naturally 
presents  itself  that  under  normal  circumstances  the  sugar-form- 
ing food-stuffs  are  altered  in  some  way  in  the  intestine  by  the 
pancreatic  juice,  and  that  this  alteration  is  a  necessary  prelimi- 
nary to  their  destruction  in  the  tissues.  Thus  absence  of  pan- 
creatic secretion  would  leave  the  sugar  undestroyed. 

It  is  quite  true  that  certain  disorders  of  digestion  occur  after 
ablation  of  the  pancreas.  The  examination  of  the  feces  of  dogs 
after  this  operation  shows  that  a  large  amount  of  fat,  proteid,  and 
starch  escapes  absorption.  This  will  not  however  serve  to  explain 
the  symptoms  of  diabetes,  since  simple  ligature  of  the  pancreatic 
duct  is  not  followed  by  any  diabetes.  Moreover  in  many  cases 
the  larger  portion  of  the  gland  has  been  excised,  and  only  a 

^Minkowski,  "Untersuch.,"  &c.,  p.  68.  Compare  Fr.  Voit,  Zeitschr.  f. 
Biol.,  vol.  xxviii.  p.  353,  and  vol.  xxix.  p.  147 :  1892. 

-  Lepine,  Wien.  lied.  Presse,  Nos.  27-32 :  1892.  Here  also  most  of  Lepine's 
previous  papers  are  quoted. 

^Hedon,  Arch.  d.  Physiol.:  April,  1892.  Compt.  rend.,  vol.  cxii,  p.  1027: 
1891 ;  and  vol.  cxv.  p.  292 :  1892. 


400  LECTURE   XXVI 

small  bit  has  been  left  free  from  all  connection  with  the  duode- 
num^ and  yet  no  glycosuria  has  been  produced.  If  fact  diabetes 
as  a  rule  occurs  only  after  complete  extirpation  of  the  gland. 
If  only  a  minute  portion  of  the  gland  be  left,  there  results  either 
no  diabetes  at  all  or  only  the  milder  form  of  this  disorder,  in 
which  sugar  disappears  from  the  urine  on  a  purely  proteid  diet 
or  during  starvation,  to  reappear  after  eating  bread.  If  the  ex- 
tirpation is  complete,  the  glycosuria  persists,  as  I  have  already 
mentioned,  in  spite  of  long-continued  inanition.  We  must  con- 
clude therefore  that  the  responsible  factor  is  not  a  disturbance 
in  the  intestinal  functions,  and  that  the  gland,  besides  the  for- 
mation of  its  secretion,  must  possess  other  functions,  which  are 
a  necessary  condition  of  normal  sugar  destruction  in  the  body. 
Before  however  we  inquire  into  the  nature  of  this  fimction, 
we  must  deal  with  an  obvious  objection  that  has  been  raised  to 
these  experiments,  viz.,  that  the  glycosuria  is  caused  by  the 
unavoidable  damage  to  neighboring  organs,  especially  the  solar 
plexus,  in  the  course  of  the  operation.  That  this  is  not  the  case 
is  shown  by  the  fact  that  any  portions  of  the  gland  may  be 
removed  piece  by  piece  without  the  occurrence  of  glycosuria. 
Only  when  the  remaining  fragment  of  the  gland  is  extirpated 
do  symptoms  of  diabetes  make  their  appearance.  Destruction 
of  the  solar  plexus  Avithout  removal  of  the  pancreas  produces, 
not  diabetes  but  only  acetonuria  and  transient  glycosuria.^  Espe- 
cially decisive  is  the  following  experiment.  The  lowest  portion 
of  the  descending  limb  of  the  pancreas  in  the  dog  is  not  con- 
nected with  the  duodenum,  but  lies  free  in  the  mesentery.  This 
piece  of  the  gland  can  be  separated  so  as  to  be  freely  movable, 
and  attached  only  by  a  long  pedicle  containing  its  artery  and 
vein.  It  can  therefore  be  taken  out  of  the  abdominal  cavity 
and  be  grafted  under  the  skin  near  the  opening  in  the  abdo- 
minal wall,  without  in  any  way  interfering  with  its  blood- 
supply.  When  the  animal  has  recovered  from  this  operation, 
the  abdominal  wound  is  again  opened,  and  the  whole  remaining 
portion  of  the  gland  extirpated,  so  that  the  animal  has  left  only 
the  small  portion  of  gland  under  the  skin  of  the  abdomen.  After 
this  operation  no  diabetes  occurs,  and  large  quantities  of  carbo- 
hydrates may  be  given  to  the  animal,  without  giving  rise  to 
glycosuria.  The  small  subcutaneous  bit  of  pancreas  prevents 
the  development  of  diabetes,  which  at  once  follows  in  all  its 
intensity  if  this  piece  be  removed.  "■  It  is  thus  possible  in  this 
way  to  produce  diabetes  in  its  severest  form  leading  to  the 
death  of  the  animal  by  a  small  operation,  which  lasts  only  a  few 
minutes  and  is  accomplished  without  opening  the  peritoneal 
^  Lustig,  Arch,  per  le  scienze  meddche,  vol.  xiii.  Fas.  2 :  1889. 


DIABETES    MELLITUS  401 

cavity,  and  in  which  there  can  be  no  suspicion  of  any  kind  of 
injury  to  adjoining  important  structures."  This  experiment 
has  been  several  times  successfully  performed  by  Minkowski, 
and  in  every  case  with  the  same  result. 

There  can  be  thus  no  doubt  that  the  pancreas  influences 
directly  or  indirectly  the  destruction  of  sugar,  and  that  this  in- 
fluence is  absolutely  independent  of  processes  which  go  on  in 
the  small  intestine.  We  must  therefore  assume  either  that  the 
sugar  of  the  blood  undergoes  some  changes  in  passing  through 
the  gland,  which  prepare  the  way  for  its  further  destruction,  or 
that  the  gland  gives  oif  some  substance  to  the  blood  and  tissues, 
which  enables  directly  or  indirectly  the  destruction  to  take  place 
in  other  organs  of  the  body. 

The  former  assumption  is  rendered  improbable  by  the  fact 
that  only  a  small  fraction  of  the  whole  blood  passes  through 
the  gland,  especially  in  the  experiments  where  the  presence 
of  a  tenth  part  of  the  whole  gland  has  prevented  the  appear- 
ance of  diabetes.  Moreover,  in  experiments  carried  out  in 
Strieker's  laboratory'  on  the  amounts  of  sugar  in  the  blood 
flowing  to  and  away  from  the  gland,  no  difference  could  be 
found. 

The  second  assumption  seems  therefore  the  only  possible 
one,  viz.,  that  the  gland  gives  off  some  substance  which  influ- 
ences the  process  of  sugar  destruction.  This  influence  might  of 
course  be  very  indirect.  We  might  imagine  for  instance  that 
the  substance  in  question  plays  a  part  in  the  functions  of  cer- 
tain portions  of  the  central  nervous  system,  and  that  the  meta- 
bolism of  the  muscles,  where  the  chief  part  of  the  sugar  is 
destroyed,  is  influenced  by  these  nerve-centers.  Analogies  for 
such  an  indirect  process  are  not  wanting,  and  I  might  remind 
my  readers  of  the  extensive  disturbances  in  the  functions  of  the 
central  nervous  system,  which  result  from  the  extirpation  of 
the  thyroid  gland,  and  which  are  prevented  so  long  as  a  piece 
of  the  gland  is  left  or  is  transplanted  into  the  abdominal  wall.^ 
We  should  thus  return  to  our  previous  hypothesis,  viz.,  that 
disturbances  in  the  functions  of  the  central  nervous  system  are 
the  cause  of  diabetes. 

I  would  however  once  more  emphasize  the  fact  that  the 
various  forms  of  diabetes  may  have  different  modes  of  causa- 
tion, and  we  need  not  assume  that  a  morbid  affection  of  the 
pancreas  is  in  all  cases  a  necessary  preliminary.  Even  if 
pathological  changes  could  be  detected  in  the  pancreas  in  all 

^Pal.,  Wien.  Min.  Wochenschr.,  No.  4:  1891. 

-A.  von  Eiselsberg,   Wien.  klin.   Wochenschr., -p.  81:  1892.    Here  the  pre- 
vious literature  is  also  quoted. 
26 


402  LECTUEE    XXVI 

cases  of  diabetes,  they  might  just  as  well  be  the  consequence  as 
the  cause  of  the  nervous  aifections. 

A  careful  microscopical  investigation  of  the  pancreas  in  all 
fatal  cases  of  diabetes  is  much  to  be  desired.  Hitherto  pathol- 
ogists have  for  the  most  part  been  satisfied  with  a  mere  inspec- 
tion of  the  organ. 

The  varying  course  and  issue  of  the  disease  seem  also  to 
show  that  there  are  many  different  forms  of  diabetes.^  We 
can  find  all  stages  between  transient  and  symptomatic  gly- 
cosuria on  the  one  hand,  and  the  chronic  variety  of  diabetes 
on  the  other.  We  occasionally  see  that  the  milder  forms  of 
chronic  diabetes  are  as  completely  cured  as  symptomatic 
glycosuria.  In  chronic  diabetes,  a  temporary  disappearance 
of  glycosuria  may,  as  we  have  already  mentioned,  be  fre- 
quently induced  by  a  withdrawal  of  carbohydrates  from  the 
food.  If  the  patient  takes  active  exercise,  a  considerable 
quantity  of  carbohydrates  may  be  borne  without  a  passage  of 
sugar  into  the  urine.  In  other  cases  again,  the  excretion  of 
sugar  continues,  although  the  food  may  consist  exclusively  of 
proteid  and  fat.  Slight  forms  of  diabetes  frequently  become 
aggravated,  and,  apart  from  this,  they  are  not  exempt  from 
fatal  complications.  The  severe  form  also  runs  a  varying 
course.  It  is  sometimes  acute,  and  death  occurs  after  a  few 
weeks,  or  it  may  be  after  a  year  or  two;  in  others,  it  may 
not  take  place  for  from  ten  to  twenty  years.  Ordinarily 
glycosuria  is  associated  with  polyuria,  the  daily  amount  of 
urine  rising  to  as  much  as  12  liters,  while  the  patients  are 
tortured  by  continual  thirst.  On  the  other  hand,  sugar  may 
appear  in  the  urine  without  polyuria  and  increased  thirst. 
Frerichs^  has  observed  more  than  thirty  cases  in  which  the 
amount  of  urine  did  not  exceed  1700  to  2000  cms.,  while  the 
quantity  of  sugar  rose  from  4  to  6,  and  even  8  per  cent.  In 
rare  cases,  diabetes  mellitus  may  pass  into  diabetes  insipidus,* 
polyuria  without  glycosuria.     In  diabetes,  death  is  caused  by 

'  Frdr.  Albin  Hoffmann  has  made  an  interesting  attempt  to  classify  and 
define  the  various  forms  of  diabetes  (  Verhandl.  d.  Congr.  für  inn.  Med.,  p.  159  : 
Fünfter  Congress,  Wiesbaden,  1886).  Compare  also  Kiilz,  loe.  cit.,  vol.  i.  p.  217  ; 
and  vol.  ii.  p.  144. 

2  Frerichs,  loc.  cit.,  p.  192. 

^  This  shows  that  polyuria  in  diabetes  mellitus  is  not  a  necessary  conse- 
quence, at  any  rate  not  in  all  cases,  of  the  glycosuria,  but  may  be  the  result  of 
a  special  nervous  disturbance.  Concerning  diabetes  insipidus,  see  Kiilz,  "  Beitr. 
zur  Pathol,  u.  Therap.  des  Diabetes  mellitus  u.  insipidus,"  vol.  ii. :  Marburg, 
1875.  The  previous  literature  on  diabetes  insipidus  is  summarized,  pp.  28-31, 
and  particularly  that  dealing  with  the  occurrence  of  inosit  in  the  urine  in  this 
disease.  Vide  Kiilz,  Sitzwngshcr.  d.  Ges.  z.  Beford.  d.  ges.  Naturw.  zu  Marburg, 
No.  4:  1876.  For  the  chemical  properties  of  inosit,  see  Maquesne,  Compt.  rend., 
vol.  civ.  pp.  225,  297  and  1719  :  1887. 


DIABETES    MELLITUS  403 

various  complications,  such  as  simple  marasmus,  pulmonary 
phthisis,  furunculosis  or  carbuncles,  nephritis,  &c.,  and  is  fre- 
quently ushered  in  by  diabetic  coma. 

I  will  dwell  upon  these  symptoms  a  little  more  fully, 
because  recent  researches  afford  a  perfectly  satisfactory  chem- 
ical explanation  of  them.  The  abnormal  constituents  of  the 
urine,  to  which  I  have  already  drawn  attention,  oxybutyric 
acid,  aceto- acetic  acid,  and  aceton,  which  may  frequently  be 
traced  in  small  quantities  during  the  earlier  stages  of  the  dis- 
ease, become  considerably  increased  in  coma.  We  shall  im- 
mediately see  that  the  cerebral  symptoms  occur  at  the  same 
time  that  these  substances  are  produced. 

A  comatose  condition  certainly  may  occur  towards  the 
close  of  the  disease,  without  these  abnormal  products  of  metab- 
olism being  formed,  but  in  these  cases  the  coma  depends  upon 
complications,  such  as  acute  cardiac  insufficiency,  cerebral  hem- 
orrhage, nephritis,  and  the  like.  But  in  most  cases,  the  above- 
named  substances  are  demonstrable  in  the  urine  in  diabetic 
coma ;  and  the  majority  of  authors  have  attributed  this  variety 
of  coma  to  their  narcotic  influence,^  especially  to  that  of  aceton, 
which  acts  in  this  respect  like  alcohol,  ether,  and  other  mem- 
bers of  this  group.  But  more  careful  experiments  showed 
that  the  narcotic  action  of  aceton  was  not  powerful  enough  to 
account  for  diabetic  coma,^  especially  if  it  be  considered  that 
aceton  arises  from  proteid,  and  that  the  amount  of  the  latter 
decomposed  is  not  sufficient  to  yield  the  quantity  of  aceton 
required  to  produce  coma. 

The  action  of  aceton  resembles  that  of  ethyl  alcohol,  but 
is  not  quite  as  powerful.  Aceton  can  be  given  to  dogs  in 
the  proportion  of  1  grm.  for  every  kilogrm.  of  body  weight 
without  any  effect.  Doses  of  4  grms.  for  every  kgrm.  cause 
symptoms  of  intoxication  with  marked  motor  disturbances, 
similar  to  those  produced  by  ethyl  alcohol.  Eight  grms.  for 
every  kgrm.  is  the  fatal  dose  of  aceton,  and  from  6  to  8  grms. 
that  of  ethyl  alcohol.^  In  order  therefore  to  poison  a  person 
weighing  70  kgrms.,  from  500  to  600  grms.  must  be  taken. 
This  amount  could  not  possibly  be  formed  from  decomposing 
pro  Leid. 

1 A  complete  summary  of  all  the  literature  on  this  subject  is  given  by  von 
Buhl,  Zeitschr.  f.  Biolog.,  vol.  xvi.  p.  413:  1880;  and  by  Rudolf  von  Jaksch, 
"  Ueber  Acetonurie  u.  Diaceturie  "  :  Berlin,  Hirschwald,  1885.  Also  Frerichs, 
loc.  CiL,  pp.  114-120. 

*  Vide  Peter  Albertoni,  Arch.  f.  exper.  Path.  w.  Pharm.,  vol.  xviii.  p.  218 : 
1884  (from  Schmiedeberg's  laboratory).  This  includes  a  complete  report  of  the 
numerous  earlier  experiments. 

3  Albertoni,  loc.  cit.,  pp.  223,  224,  226. 


404  LECTURE    XXVI 

That  diabetic  coma  does  not  result  from  the  narcotic 
action  of  aceton  is  further  proved  by  the  fact  already  stated, 
that  the  amount  of  aceton  in  the  urine  sometimes  diminishes 
during  the  stage  of  coma,  while  there  is  an  increase  in  its  pre- 
cursor, oxybutyric  acid,  which  has  no  paralyzing  influence  on 
the  brain/ 

Stadelmann^  and  Minkowski^  have  however  offered  a 
satisfactory  explanation  of  this  condition.  They  refer  it  to 
a  saturation  of  the  alkalies  in  the  blood  by  the  products  of 
incomplete  combustion,  which  are  of  an  acid  nature  like 
oxybutyric  acid.  The  symptoms  of  diabetic  coma  are  in  fact 
similar  to  those  observed  by  Fr.  Walter*  in  animals,  which 
he  poisoned  with  mineral  acids.  When  dilute  hydrochloric 
acid  was  injected  into  the  stomach  of  a  rabbit,  dyspnea 
occurred,  the  animal  lost  the  power  of  motion,  and  died  with 
all  the  signs  of  collapse.  But  if  carbonate  of  soda  were  sub- 
cutaneously  injected  after  the  symptoms  of  poisoning  had 
set  in,  the  animals  recovered.  Walter  estimated  the  car- 
bonic acid  in  the  blood  of  animals  which  had  been  poisoned 
with  acids,  and  found  only  from  2  to  3  per  cent,  by  volume. 
This,  as  I  have  shown  in  our  remarks  on  the  gases  of  the 
blood  (p.  262),  is  the  amount  of  carbonic  acid  which  is 
simply  dissolved  in  the  blood.  Consequently  the  blood  of  the 
poisoned  animals  contained  no  alkalies  that  could  fix  the 
carbonic  acid,  as  they  had  been  saturated  with  the  hydro- 
chloric acid.^  It  follows  that  the  blood  had  been  deprived 
of  the  carrier  of  the  carbonic  acid,  which  consequently  ac- 
cumulated in  the  brain,  and  produced  the  usual  symptoms. 
Walter  has  also  demonstrated,  as  I  have  mentioned,  that  the 
administration  of  acids  increases  the  amount  of  ammonia  in 
the  urine.  Very  similar  phenomena  are  observed  in  diabetic 
coma.  The  eifect  of  hydrochloric  acid  in  the  experiments  on 
animals  is  identical  with  that  of  oxybutyric  acid  in  diabetic 
coma.  Here  also  dyspnea  is  a  symptom  ;  the  diabetic  also 
shows  an  increase  of  ammonia  in  the  urine,  and  this  increase 

*  Wolpe,  "  Unters,  über  die  Oxybuttersäure  des  diabetischen  Harnes,"  Dis- 
sert. :  Königsberg,  1886  ;  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxi.  p.  138 :  1886 ; 
and  O.  Minkowski,  Mittheilungen  aus  der  medicin.  Klinik  zu  Königsberg,  vol. 
xvii.  p.  443:  1883. 

2  E.  Stadelmann,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xvii.  p.  443  :  1883. 

ä  O.  Minkowski,  loc.  cit. 

Tr.  Walter,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  vii.  p.  148:  1877  (from 
Schmiedeberg's  laboratory). 

s  Walter  ( loc.  cit. )  speaks  of  withdrawal  of  alkali,  which  has  not  been  proved 
by  his  experiments.  The  alkalies  that  are  saturated  by  the  acid  may  remain  in 
the  blood  as  neutral  salts,  until  the  kidneys  have  excreted  the  acid,  leaving  the 
bases  in  the  blood. 


DIABETES    MELLITUS  405 

reaches  tlie  highest  point  in  the  stage  of  coma.^  Minkowski 
has  also  determined  the  amount  of  carbonic  acid  in  the 
blood  of  a  comatose  diabetic  patient,  and  has  only  found  a 
volume  percentage  of  3.3.  The  blood  had  been  taken  a  short 
time  before  the  death  of  a  patient  from  his  radial  artery.^ 
Blood  taken  from  the  dead  body  had  a  distinctly  acid  reac- 
tion, and  contained  large  quantities  of  oxybutyric  and  sarco- 
lactic  acids. 

Finally,  I  may  be  permitted  to  make  a  few  remarks  on  the 
treatment  of  diabetics  from  the  chemical  point  of  view. 

So  long  as  the  causes  of  the  diiferent  forms  of  diabetes  are 
unknown  to  us,  there  can  be  no  question  of  a  rational  mode  of 
cure.  We  can  do  nothing  more  than  relieve  the  most  painful 
symptoms. 

It  has  been  quite  right  to  try  and  reduce  the  amount  of 
undecomposed  sugar  in  the  body,  not  only  because  it  is  useless, 
but  because  its  circulation  induces  disturbances  in  all  the 
tissues,  and  because  certain  organs,  especially  the  kidneys,  are 
overworked,  and  a  tormenting  thirst  is  induced.  On  this 
ground,  muscular  work  is  strongly  to  be  recommended.  Kiilz,^ 
as  we  have  already  remarked,  has  shown  that  in  many  cases 
muscular  exertion  materially  diminishes  the  excretion  of  sugar. 
Bouchardat  asserts  that  he  has  obtained  permanent  improve- 
ment in  many  cases  by  this  method.  It  does  not  answer  in  all 
cases,  a  circumstance  which  also  tends  to  prove  the  existence  of 
different  forms  of  diabetes. 

If  we  desire  to  reduce  the  amount  of  carbohydates,  we 
must  be  prepared  with  a  substitute.  A  diet  consisting  exclu- 
sively of  proteid  is  objectionable,  because  it  gives  rise  to 
acetonuria,  and  increases  the  danger  of  coma.  So  long  as  the 
theory  prevailed  that  diabetes  consisted  essentially  in  an  in- 
ability to  decompose  the  sugar,  it  was  sought  to  introduce  the 
products  of  decomposition  with  the  food.  But  we  are  not 
acquainted  with  the  intermediate  products  of  the  decomposition 
of  sugar,  and  even  if  they  were  known  to  us,  we  could  not 
replace  the  sugar  by  introducing  them,  because  at  the  moment 
of  decomposition  kinetic  energy  is  liberated,  which  is  utilized 
in  the  performance  of  muscular  and  other  functions.     Never- 

^  Minkowski,  loc.  cit.,  p.  179. 

2  I  must  refer  to  the  extremely  interesting  original  work  for  the  details  of 
this  experiment.  It  also  contains  important  critical  observations  on  recent  liter- 
ature of  diabetes. 

3  Kiilz,  loc.  cit.,  vol.  i.  pp.  179-216  (where  the  older  statements  of  Trousseau 
and  Bouchardat  are  quoted),  and  vol.  ii.  pp.  177-180.  Also  Dr.  Carl  Zimmer, 
"  Die  Muskeln  eine  Quelle,  Muskelarbeit  ein  Heilmittel  bei  Diabetes  ":  Karlsbad, 
1880;  and  von  Mering,  Verhandl.  d.  Congresses  f.  innere  3Iedicin,  p.  171  :  Wies- 
baden, 1886. 


406  LECTUEE    XXVI 

theless,  some  physicians  have  thought  that  the  daily  administra- 
tion of  from  5  to  10  grms.  of  lactic  acid  would  serve  as  a  sub- 
stitute for  the  300  to  800  grms.  of  carbohydrates  required  by 
an  adult  !  Larger  quantities  of  lactic  acid  cannot  be  given, 
because  they  would  disturb  the  digestion. 

Acting  on  an  erroneous  supposition  of  O.  Schultzen/  who 
imagined  glycerin  to  be  one  of  the  normal  products  of  the  de- 
composition of  sugar,  they  have  tried  to  replace  sugar  by 
glycerin.  The  latter  has  the  advantage  over  lactic  acid  of 
its  sweet  taste,  but  only  a  very  small  quantity  can  be  pre- 
scribed. After  larger  doses  diarrhea  occurs,  and  a  part  of 
the  absorbed  glycerin  passes  unaltered  into  the  urine  (vide 
supra,  p.  362).^  Glycerin  should  therefore  be  given  in  its 
natural  form  as  fat.^  Fats  can  be  digested  very  well  by 
diabetics  (vide  supra,  p.  388),  and  are  the  best  substitutes  for 
the  carbohydrates.* 

Many  attempts  have  been  made  lately  to  administer  levo- 
rotatory  sugar  to  diabetics.  C.  A.  Socin,*  however,  as  the  re- 
sult of  a  careful  experiment,  gives  an  emphatic  warning  against 
this  treatment.  He  finds  that  in  the  mild  form  of  diabetes  thä 
levorotatory  sugar  is  at  first  destroyed,  but  the  body  rapidly 
loses  this  power.  The  same  result  is  observed  after  the  admin- 
istration of  small  quantities  of  dextrorotatory  sugar,  for  which, 
even  in  the  mild  form  of  the  disease,  patients  soon  lose  their 
tolerance. 

It  is  well  known  that  essential  improvement  in  the  condition 
of  diabetics,  especially  with  regard  to  the  elimination  of  sugar, 
is  effected  by  the  use  of  alkaline,  and  particularly  of  Carlsbad, 
water  in  the  water-cures.  It  was  thought  that  the  increased 
alkalescence  of  the  blood  favored  combustion  {vide  supra,  p. 
247).  This  explanation  appears  still  more  probable  if  we  con- 
sider the  abnormal  acids  which  occur  in  the  blood  of  diabetics. 
But  it  has  been  proved  by  direct  experiments  that  the  mere 
administration  of  carbonates  of  alkalies  without  the  mode  of 


*0.  Schultzen,  Berliner  Hin.  Wochenschr.,  No.  35  :  1872. 

*  To  satisfy  the  sense  of  taste,  saccharin  has  recently  been  introduced  as  a 
substitute  for  sugar.  With  regard  to  the  experiences  of  its  use,  see  E.  Kohl- 
echiitter  und  M.  Elsässer,  Arch.  f.  klin.  Med.,  vol.  xli.  p.  178  :  1887 ;  and  the 
article  "  Saccharin,"  by  T.  Stevenson  and  L.  C.  Wooldridge,  in  the  Lancet, 
November  17,  1888. 

3  Considerable  variety  and  change  of  diet  may  be  effected  in  the  way  of  fats 
with  fat  fish,  of  which  a  number  are  easy  of  digestion,  yolk  of  egg,  fresh  cream 
(one-half  of  its  small  production  of  milk-sugar  being  utilized  by  diabetics), 
almonds,  nuts,  cocoa,  and  olives. 

"*  Pettenkofer  and  Voit,  Zeitschr.  f.  Biolog.,  vol.  ill.  p.  441 ;  1867. 

^  C.  A.  Socin,  "  Wie  verhalten  sich  Diabetiker,"  <fec.,  Dissert.,  Strassburg  : 
1894. 


DIABETES   MELLITUS  407' 

life  adopted  at  watering-places,  does  not  diminish  the  excretioil 
of  sugar.^ 

So  far  the  attempts  to  subdue  diabetic  coma  by  the  injection 
of  carbonate  of  soda  into  the  blood  have  remained  without  any- 
favorable  results.^  We  cannot  expect  to  obtain  any  real  im- 
provement from  the  addition  of  alkalies,  because  this  mode  of 
treatment  deals  only  with  the  symptoms,  and  not  with  the  cause 
of  the  disease. 

^  Frerichs,  loc.  cit.,  p.  263.  Nencki  and  Sieber,  Journ.  f.prakt.  Chem.,  vol. 
xxvi.  p.  33:  1882.  Also  Külz,  loc.  cit.,  vol.  i.  31 ;  ii.  154.  A  summary  of  all  the 
earlier  literature  will  be  found  here. 

2  O.  Minkowski,  Mittheilungen  aus  der  medicinischen  Klinik  zu  Königsberg, 
i.  Pr.,  pp.  183-186 :  1888. 


LECTURE   XXVII 

INFECTION 

The  time-worn  controversy  as  to  the  origin  of  infectious 
diseases,  whether  they  are  brought  about  by  living  organisms 
— the  "  contagium  vivum/'  or  simply  by  poisons,  i.  e.,  definite 
chemical  substances,  has  been  finally  settled  by  the  unceasing 
labors  of  the  last  two  or  three  decades  in  favor  of  the  former 
alternative.  We  know  that  the  various  infectious  diseases  are 
due  to  the  entry  of  different  and  definite  bacteria  into  the  tissues 
of  our  body. 

Now  however  arises  the  further  question  :  Are  the  symp- 
toms of  these  diseases  the  result  of  the  mechanical  disturbances 
caused  by  the  spread  of  the  bacteria  through  the  tissues,  or  have 
we  to  do  with  the  poisonous  products  of  metabolism  ?  And  the 
conviction  is  growing  more  and  more  clear  that  the  latter  theory 
is  the  right  one.^ 

We  may  cite  the  following  proofs  in  support  of  this  con- 
tention : 

1 .  In  certain  infectious  diseases  the  pathogenic  organisms  do 
not  penetrate  into  the  internal  organs,  but  remain  in  the  super- 
ficial mucous  membranes,  as  in  the  case  of  diphtheria,  or  in  the 
surface  of  the  wound,  as  in  tetanus.  And  yet  in  all  these  mal- 
adies, a  general  intoxication  ensues. 

2.  Certain  pathogenic  bacteria  may  be  cultivated  outside  the 
body  in  artificial  nutrient  fluids.  Such  a  fluid  can  then  be  com- 
pletely freed  from  bacteria  by  filtration,  and  the  filtrate,  when 
injected  into  the  body  of  a  healthy  animal,  will  produce  symp- 
toms of  poisoning  similar  to  those  which  would  result  if  the 
bacteria  themselves  were  inoculated.     ( Vide  infra.) 

The  adherents  of  the  theory  of  "  living  contagion  "  had  now 
the  same  duty  to  perform  which  had  previously  fallen  to  the  lot 
of  its  opponents,  i.  e.,  of  isolating  the  poisons,  of  preparing 
them  as  chemical  entities,  investigating  their  characteristics  and 
studying  their  behavior  towards  the  constituents  of  the  tissues. 
The  morphologist  had  done  his  part ;  the  chemist  must  now 
intervene. 

■•  An  account  of  the  earlier  literature  on  this  subject  is  given  by  P.  L.  Panum, 
Virchow's  Arch.,  vol.  Ix.  p.  301 :  1874. 

408 


INFECTION  409 

The  poison  was  first  thought  to  belong  to  the  nitrogenous 
organic  bases,  the  alkaloids.  This  supposition  was  favored  by 
the  facts  that  the  most  intense  organic  poisons  belong  to  the 
group  of  alkaloids,  and  that  moreover  nitrogenous  bases  may 
result  from  the  metabolism  of  the  bacteria.  Poisonous  bases 
readily  arise  from  the  decomposition  of  proteids,  of  the  nu- 
cleins,  or  by  a  conversion  of  the  nitrogenous  bases  preformed 
in  the  animal  tissues,  such  as  creatin,  cholin,  and  the  xanthin 
bodies. 

The  first  attempt  to  isolate  the  poisonous  bases  produced  by 
bacterial  putrefaction  was  made  by  Bergmann  and  Schmiede- 
berg,^  who  prepared  in  a  crystalline  form  the  sulphate  of  an 
organic  base  from  putrid  yeast.  When  injected  into  a  dog,  0.01 
gr.  of  these  crystals  produced  vomiting  and  bloody  diarrhea. 

Of  the  numerous  and  more  recent  experiments  conducted 
with  the  object  of  isolating  poisonous  alkaloids  from  the  bac- 
terial products  ^  I  will  only  select  those  where  a  clearly  defined 
chemical  individual  has  been  obtained,  which  has  been  proved 
to  be  acutely  poisonous. 

L.  Brieger^  prepared  from  putrid  meat  and  fish  two  bases, 
which  are  closely  allied  to  cholin  and  had  probably  been  formed 
from  the  cholin  which  occurs  in  the  form  of  lecithin  in  all 
animal  tissues.  One  of  these  two  bases  was  neurin ;  the  other 
was  isomeric  with  muscarin.  (  Vide  Lect.  VI.  p.  76.)  The  neu- 
rin proved  to  be  identical  with  that  synthetically  prepared  by 
Hofmann  *  and  von  Baeyer,^  which  is  distinguished  from  cholin 
by  the  possession  of  one  less  molecule  of  water.  It  must  there- 
fore be  regarded  as  trimethyl-vinyl-ammonium  hydroxid  : 


1 E.  Bergmann  and  O.  Schmiedeberg,  Centralbl.  f.  d.  med.  Wissensch.,  p.  497  : 
1868.    Bergmann,  Deutsch.  Zeitschr.  f.  Chirurgie,  vol.  i.  p.  373  :  1872. 

2  The  comprehensive  literature  on  this  subject  is  quoted  by  F.  Gräbner, 
"  Beitr.  z.  Kenntniss  der  Ptomaine,"  Diss.,  Dorpat :  1882.  M.  Nencki,  Journ.  f. 
prakt.  Chem.,  N.  F.,  vol.  xxvi.  p.  47  :  1882.  L.  Brieger,  "  Ueber  Ptomaine," 
Berlin,  Hirschwald,  1885.  "  Weitere  Unt.  üb.  Ptomaine,"  1885.  "  Unt.  üb. 
Ptomaine."  Dritter  Theil,  1886,  and  Virchow's  Arch.,  vol.  civ.  p.  483  :  1889. 
Compare  also  F.  Selmi,  "  SuUe  ptomaine  ed  alcaloidi  cadaverici  e  loro  importanza 
in  tossicologia,"  Bologna  :  1878,  and  Gau  tier,  "  Cours  de  Chimie,"  "  Chimie 
biologique,"  Paris,  pp.  261-270  :  1892. 

^L.  Brieger,  "Ueber  Ptomaine,"  Berlin,  Hirschwald,  pp.  34^36  and  p.  48 : 
1885. 

*A.  W.  Hofmann,  Compt.  rend.,  vol.  xlvii.  p.  558  :  1858. 

^  Baeyer,  Ann.  d.  Chem.  u.  Pharm.,  vol.  cxl.  p.  311  :  1866. 


410  LECTUEE    XXVII 

Both  bases  produced  toxic  effects  similar  to  those  of  the 
muscarin  prepared  from  fly-fungus.  Besides  the  above- 
mentioned,  Brieger'  obtained  from  putrid  meat,  cheese  and 
gelatin  (in  small  quantity  also  from  fresh  eggs  and  fresh 
human  brain),  a  base  with  the  empirical  composition  C^Hj^Nj,, 
the  constitution  of  which  could  not  be  thoroughly  ascertained. 
On  boiling  with  potash  it  gave  off  dimethylamin  and  trimethyl- 
amiu.  Brieger  gave  it  the  name  of  neuridin.  This  base  again 
produced  in  frogs  and  rabbits  symptoms  of  poisoning  similar  to 
those  caused  by  muscarin,  and  2  mg.  of  the  hydrochlorate  of 
this  base,  when  injected  into  the  dorsal  lymph -sac  of  a  frog 
proved  fatal.  In  rabbits  the  lethal  dose  was  0.04  g.  per 
kilo,  bodyweight. 

Another  base,  methyl-guanidin,  was  isolated  by  Brieger  ^  in 
small  amounts  from  horse  flesh  which  had  been  undergoing 
putrefaction  for  four  months  : 

The  poisonous  character  of  this  compound  had  already  been 
remarked  by  Baumann  and  Gergens  ^ :  1  mg.  injected  into  the 
dorsal  lymph-sac  of  a  frog  gave  rise  to  definite  toxic  manifesta- 
tions, consisting  in  fibrillar  twitchings  of  the  dorsal  muscles ; 
larger  doses  brought  on  convulsive  movements  of  the  extrem- 
ities, which  frequently  became  tetanic  in  character ;  0.05  g. 
caused  death,  which  occurred  after  the  muscular  symptoms  had 
lasted  for  some  time,  occasionally  for  as  much  as  three  days. 
Brieger  made  a  subcutaneous  injection  of  0.2  g.  of  methyl- 
guanidin  prepared  from  putrid  meat  into  a  guinea-pig,  which 
at  once  became  paralyzed  in  the  limbs  and  died  twenty  minutes 
afterwards  with  general  clonic  convulsions.  We  may  assume 
that  the  methylguanidin  was  probably  formed  from  the  creatin 
of  the  meat.     (See  page  298.) 

I  shall  not  give  any  account  of  the  numerous  other  bases, 
which  have  been  isolated  from  bacterial  products,  since  some 
of  these  (such  as  mydalein,  typhotoxin,  mydatoxin,  gadinin^ 
&c.)  have  not  been  obtained  in  a  pure  state,  or  if  they  have, 
in  such    small  amounts    that    their    chemical    properties  and 

1  Brieger,  loc.  cit.,  pp.  20-30,  51,  64,  57,  61. 

2  Brieger,  "  Uat.  üb.  Ptomaine,"  Dritter  Theil,  Berlin,  1886,  p.  34,  et  seq. 
Compare  Hofifa,  Sitzungsber.  d.  phys.  med.  Ges.  zu  Würzburg,  pp.  101  and  102  : 
1889. 

^  Baumann  and  Gergens,  Pfilüger's  Arch.,  vol.  lii.  p.  205  :  1876. 


INrECTION  411 

physiological  effects  could  not  be  properly  tested.  On  the 
other  hand  others,  such  as  methylamin,  dimethylamin,  trime- 
thylamin,  tetramethylendiamin  (putrescin),  pentamethylendia- 
min  (cadaverin),  &g.,  have  been  found  to  be  quite  innocuous. 
The  investigation  of  the  last-mentioned  products  forms  a 
valuable  contribution  to  the  material  for  a  future  physiology  of 
bacterial  metabolism.^  But  so  far  it  has  added  nothing  to 
our  knowledge  of  the  etiology  and  symptoms  of  infectious 
diseases. 

In  the  case  of  the  poisonous  bases,  there  is  not  always 
sufficient  evidence  that  the  poison  is  due  to  the  bases  them- 
selves and  not  merely  to  the  impurities  in  them.  Researches 
up  to  the  present  seem  to  show  that  the  more  carefully  the 
bases  are  purified,  the  less  action  do  they  have  on  the  animal 
body.  It  is  greatly  to  be  desired  that  in  ftiture  all  investiga- 
tion on  the  metabolic  products  of  microorganisms  should  be 
confined  to  "  pure  cultures,"  both  with  the  object  of  obtaining 
an  insight  into  bacterial  changes  as  well  as  for  the  purpose  of 
increasing  our  knowledge  of  the  etiology  of  infectious  diseases. 
In  this  way  it  could  always  be  definitely  ascertained  by  which 
species  of  bacteria  the  material  under  examination  was  formed. 
Another  point  of  great  importance  is  that  the  chemical  compo- 
sition of  the  nutrient  medium  before  the  introduction  of  the 
bacteria  should  be  accurately  determined.  A  beginning  to  in- 
vestigations of  so  exact  but  laborious  a  nature  has  already  been 
made  by  Brieger/  Roux  and  Yersin/  Löffler,*  Kitasato  and 
Weyl/  Tizzoni  and  Cattani,^  Nencki  and  his  pupils,  besides 
others. 

If  we  now  proceed  to  inquire  whether  the  symptoms  of 
infectious  diseases  may  really  be  explained  from  the  known 
toxic  effects  of  the  bases  which  have  been  isolated  from  the 
bacterial  products,  we  must  acknowledge  at  once  that  it  is 
impossible   to  expect   any  absolute  agreement.      We  may  in- 

^  To  this  group  belongs  also  the  compound  isomeric  with  collidin,  which 
Nencki  prepared  from  putrid  gelatin,  and  which  was  the  first  of  the  organic  bases 
isolated  from  bacterial  products.  Nencki,  "  Ueb.  die  Zersetzung  der  Gelatine  und 
des  Eiweisses  b.  d.  Fäulniss  mit  Pankreas,"  Festschrift,  Bern.  p.  17:  1876.  See 
also  S.  Adeodato  Garcia,  Zeitschr.  f.  physiolog.  Chem.,  vol.  xvii.,  pp.  543-595 : 
1893. 

2  Brieger,  "  Weitere  Unt.  üb.  Ptomaine,"  Berlin,  1885,  p.  67,  et  seq.,  and 
"  Unt  üb.  Ptomaine,"  Dritter  Theil,  p.  84,  et  seq.:  1886. 

*  E.  Roux  et  A.  Yersin,  Annales  de  V Institut  Pasteur,  Annee  ii.,  p.  642 : 
1888. 

■^F.  'Lö^QY,  Deutsch,  med.  Wochenschr.,  Jahrgang  16,  p.  109:  1890. 
5  S.  Kitasato  u.  Th.  Weyl,  Zeitschr.  f.  Hygiene,  vol.  viii.  p.  404 :  1890,  and 
Kitasato,  idem,  vol.  x.  p.  267  :  1891. 

*  Tizzoni  u.  Cattani,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxvii.  p.  432: 
1890. 


412  LECTURE   XXVII 

deed  anticipate  the  direction  in  which  the  main  differences 
will  lie. 

In  the  first  place,  the  artificial  production  of  the  disease  by 
the  injection  of  a  substance  already  prepared  from  the  patho- 
genic microorganisms,  does  away  with  the  first  characteristic 
of  all  zymotic  disease — that  of  incubation.  If  the  infection  is 
caused  by  the  entrance  of  a  small  number  of  bacteria,  a  certain 
time  must  naturally  elapse  before  these  can  increase  and  enter 
the  circulation  and  the  chief  organs,  to  the  disturbance  of  whose 
functions  the  salient  symptoms  of  the  disease  are  due.  Whereas 
with  the  injection  of  a  poison  —  especially  of  such  a  poison  as 
the  bases  of  a  soluble  salt — the  disturbances  must  commence 
at  once,  and  the  whole  series  of  symptoms  must  run  a  more 
rapid  course.  Further,  we  must  not  forget  that  the  injected 
poison  does  not  necessarily  reach  all  the  organs,  tissues,  and 
cells  which  the  bacteria  do,  and  that  on  the  other  hand,  the 
bacteria  may  not  enter  all  the  parts  where  the  poison  may 
penetrate  by  diffusion.  Finally,  we  must  take  into  considera- 
tion that  there  is  probably  more  than  one  poisonous  product 
from  each  species  of  pathogenic  microbes,  and  that  the  various 
symptoms  of  any  given  zymotic  disease  may  be  caused  by  dif- 
ferent poisons,  or  by  a  combination  of  two  or  more  poisons. 
The  artificial  injection  of  a  chemical  individual  might  not  pro- 
duce these  identical  symptoms. 

But  even  when  we  have  made  every  allowance  for  possible 
differences,  it  remains  improbable  that  the  alkaloids  of  putre- 
faction which  have  up  to  the  present  time  been  examined,  are 
responsible  for  the  symptoms  of  the  various  infectious  diseases, 
for  the  reason  that  they  are  not  nearly  poisonous  enough.  We 
must  remember  that  the  body  possesses  in  a  marked  degree  the 
faculty  of  getting  rid  of  injurious  substances  of  all  kinds  as  they 
are  formed.  In  seeking  an  explanation  for  the  symptoms  of 
zymotic  disease  we  may  therefore  restrict  ourselves  to  the  poisons 
of  great  virulence. 

The  toxic  action  of  the  alkaloids  of  putrefaction,  of  the 
so-called  ptomains  and  toxins,  has  been  much  exaggerated, 
because  small  animals,  and  especially  mice,  were  used  for  the 
experiments.  Now  we  must  not  forget  that  the  bodyweight 
of  a  mouse  is  only  about  10-17  g.  If  for  example  we  take 
tetanin — a  base  which  was  first  isolated  by  Brieger  from  the 
metabolic  products  of  the  tetanus  bacilli,  and  considered  to  be 
the  specific  tetanus  poison  —  we  find  that  3  eg.  of  the  hydro- 
chlorate  is  necessary  to  kill  a  mouse  when  subcutan eously 
injected,  i.  e.,  2-3  g.  per  kilo,  bodyweight.  In  the  case  of  a 
guinea-pig  (about  |  kilo.)  0.5  g.  (therefore  1  g.  per  kilo.)  had 


INFECTION  413 

"  but  little  eß'ect "  siibcutaneously  ;  the  animal  did  not  succumb/ 
Whereas,  according  to  Tizzoni  and  Cattani/  y^th  drop  of  the 
tetanus  cuture  filtrate,  i.  e.,  of  the  nutrient  fluid  from  which 
the  tetanus  bacilli  had  been  entirely  removed  by  filtration,  was 
sufficient  to  cause  the  death  of  medium-sized  rabbits  from 
tetanus.  Vaillard  and  Vincent  ^  state  that  1  ccm.  of  the  filtered 
culture  of  the  tetanus  bacilli  in  broth  contained  only  0.025  g. 
organic  matter,  and  that  this  amount  —  of  which  the  poison 
formed  but  a  fraction  —  was  enough  to  kill  a  thousand  guinea- 
pigs,  or  a  hundred  thousand  mice  ! 

Similar  observations  have  also  been  made  with  other  pure 
cultivations  of  pathogenic  bacteria.  The  fluids  in  which  the 
bacteria  have  lived  contain  poisons  of  far  greater  virulence  than 
the  alkaloids  which  have  been  isolated  from  them. 

Ceaseless  endeavors  have  during  the  last  few  years  been 
made  to  investigate  these  powerful  poisons.  Here  again  the 
same  difficulties  were  met  with  as  in  the  attempt  to  isolate 
ferments  (vide  Lecture  XI.  p.  159).  The  toxic  substances 
cannot  be  separated  from  certain  proteids.  The  first  author, 
who  came  to  the  conclusion  that  the  poison  produced  by  the 
bacteria  "  clung  to  the  proteids  "  was  Panum.*  He  says  :  "  It 
almost  seems  as  if,  led  away  by  the  desire  to  find  a  crystallized 
body,  the  investigator  had  overlooked  the  fact  that  impurities 
with  crystallized  foreign  substances  are  as  much  impurities  as 
the  presence  of  substances  which  prevent  the  crystallization  of 
a  body.^ 

Roux  and  Yersin^  filtered  broth  cultivations  of  diphtheria 
bacilli  through  clay  cells  :  the  filtrate  was  still  effective,  2  cm. 
killing  a  rabbit  when  injected  subcutaneously.  But  it  proved 
inoperative  after  being  heated  for  ten  minutes  to  100°  C:  35 
ccm.  could  be  injected  directly  into  the  vein  of  a  rabbit  with- 
out any  injurious  consequences.  These  authors  therefore  imag- 
ine that  the  active  constituent  might  be  of  a  nature  similar 
to  that  of  the  hydrolytic  ferments.  In  common  with  the  fer- 
ments, it   likewise   possessed    the   property    of  being   carried 

1  S.  Kitasato  u.  Th.  Weyl,  Zeitschr.  /.  Hygiene,  vol.  viii.  p.  407 :  1890. 

''■  Tizzoni  u.  Cattani,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxvii.  p.  437  :  1890. 
Compare  also  S.  Kitasato,  Zeitschr.  f.  Hygiene,  vol.  x.  p.  267 :  1891. 

2  Vaillard  et  Vincent,  Annates  de  P Institut  Pasteur,  Ann.  V.  p.  15 :  1891. 

■*Panum,  "Bibliothek  for  Laeger,"  vol.  viii.  pp.  253-285:  1856.  Summa- 
rized in  Schmidt's  Jahrb.,  pp.  213-217:  1859;  and  Virchow's  Arch.,  vol.  Ix.  p. 
334:  1874. 

5  Virchoiv's  Arch.,  vol.  Ix.  p.  332 :  1874. 

6  E.  Roux  et  A.  Yersin,  Ann.  de  V Institut  Pastetcr,  Annee  II.  p.  642:  1888; 
and  Annee  III.  p.  273 :  1889.  Compare  S.  Dzierzgowski  et  L.  de  Rekowski, 
Arch.  d.  Sciences  Biolog.,  publ.  par  I'Institut  imperial  de  Med.  exp.  a  St.  Peters- 
bourg,  vol.  i.  p.  167  :  1892. 


414  LECTURE    XXVII 

down  by  neutral  precipitates  such  as  phosphate  of  lime.  Sub- 
cutaneous injection  of  0.02  g.  of  such  a  moist  precipitatCj  con- 
taining less  than  0.0002  g.  of  organic  substance,  killed  a 
guinea-pig  in  the  space  of  four  days.  The  poison,  although 
capable  of  being  dialyzed,  has  no  eifect  when  taken  into  the 
stomach. 

Löffler  ^  was  able  to  obtain  the  active  toxic  principle  from 
meat-broth  in  which  a  pure  culture  of  diphtheria  bacilli  had 
been  made,  by  the  same  method  usually  employed  for  isolating 
ferments  :  i.  e.,  extraction  with  glycerin  and  precipitation  with 
alcohol.  The  poison  thus  obtained,  when  injected  subcutane- 
ously  into  guinea-pigs,  occasioned  the  same  local  symptoms  as 
did  the  inoculation  with  the  bacilli  themselves. 

L.  Brieger  and  C.  Fränkel  ^  made  similar  experiments  with 
cultures  of  diphtheria,  typhus,  tetanus,  and  cholera  bacteria, 
with  staphylococcus  aureus,  with  watery  extracts  from  the 
organs  of  animals  which  had  died  of  anthrax.  They  invari- 
ably found  that  the  toxic  properties  were  associated  with 
certain  proteid  precipitates,  which  were  thrown  down  on  the 
addition  of  alcohol  or  of  a  concentrated  solution  of  ammonium 
sulphate.  If  heated  above  60°  C.  the  substances  were  ren- 
dered innocuous,  although  they  withstood  evaporation  to  dryness 
at  50°. 

Wassermann  and  Proskauer  ^  repeated  these  experiments  of 
Brieger  and  Fränkel,  and  prepared  proteid  precipitates  from  the 
filtrates  from  pure  cultivations  of  diphtheria  bacilli.  About  10 
mg.  of  such  a  precipitate  injected  under  the  skin  killed  a  rabbit 
in  about  3  to  4  days. 

Tizzoni  and  Cattani  *  precipitated  a  proteid  with  sulphate  of 
ammonia  from  the  filtrate  of  pure  cultivations  of  tetanus 
bacilli.  4  mg.  of  this  proteid  precipitate  injected  subcuta- 
neously  killed  a  rabbit  weighing  2  kg.  with  "  all  the  signs  of 
tetanus." 

From  filtered  cultures  of  the  same  bacillus,  Vaillard  and 
Vincent*  also  obtained  a  proteid,  which  was  either  thrown 
down  from  watery  solutions  by  alcohol,  or  was  carried  down  by 
neutral  precipitates  such  as  phosphate  of  lime.  This  proteid, 
however    was    less   poisonous    than    the   filtrate   of   the   pure 

'  Löffler,  Deutsch,  med.  Wochenschr.,  Jahrg.  16,  p.  109:  1890. 

^  L.  Brieger  and  C.  Fränkel,  Berlin.  Hin.  Wochenschr.,  Jahrg.  27,  pp.  241 
and  268  :  1890. 

3  A.  Wassermann  and  B.  Proskauer,  DeiUsch.  med.  Wochenschr.,  Jahrg.  17, 
p.  585:  1891. 

^  Tizzoni  and  Cattani,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxvii.  p.  447  :  1890. 

5  L.  Vaillard  and  H.  Vincent,  Ann.  d.  l'Institut  Pasteur,  Annee  V.  pp.  15, 
19-20:  1891. 


INFECTION  415 

cultures  from  which  it  was  prepared.  Of  the  latter  an  amount 
containing  only  0.000025  g.  of  organic  substance  sufficed  to  kill 
a  guinea-pig,  whereas  it  took  0.00015  g.,  or  six  times  more  of 
the  proteid  precipitate,  to  produce  the  same  effect.^  In  the 
various  procedures  adopted  for  isolating  the  toxin  therefore  it 
has  become  partially  destroyed.  Kitasato  was  likewise  unsuc- 
cessful in  obtaining  a  precipitate  which  was  more  poisonous 
than  the  filtered  cultures  from  which  he  started.  Here  again 
we  have  an  analogy  with  the  hydrolytic  ferments.  Fresh  gas- 
tric and  pancreatic  juices  or  freshly  prepared  extracts  from  the 
gastric  mucous  membrane  or  pancreas  are  always  more  active 
than  the  ferments  isolated  from  them.  The  poisonous  products 
of  bacteria  are  therefore,  like  the  hydrolytic  ferments,  ex- 
tremely labile  compounds.  The  same  observation  was  made 
by  Wassermann  and  Proskauer.^ 

Among  the  products  excreted  by  the  tubercle  bacillus  there 
is  likewise  a  substance  which  is  precipitated  by  alcohol  or  by  a 
concentrated  solution  of  ammonium  sulphate  and  dissolves  again 
in  water.  On  addition  of  acetic  acid  and  sodium  chlorid  to  the 
watery  solution,  a  precipitate  is  thrown  down  which  disappears 
on  heating.  The  substance  is  diffusible ;  it  is  soluble  in  gly- 
cerin, and  may  be  precipitated  from  this  solution  by  alcohol. 
The  toxic  eifect  is  connected  with  this  substance  which,  to  judge 
from  its  reactions,  belongs  to  the  precursors  of  proteid,  the  so- 
called  albumoses.  The  subcutaneous  injection  of  a  small 
amount  (about  1  mg.)  into  a  healthy  person  caused  a  rise  of 
temperature  to  39.1°  C. ;  in  a  woman  suffering  from  lupus,  an 
amount  five  times  less  produced  a  rise  to  40.4°  C.^ 

From  a  pure  cultivation  of  streptococcus  pyogenes,  N. 
Sieber*  obtained  an  albumose  precipitate,  of  which  0.013  g. 
injected  under  the  skin  of  a  rabbit  caused  the  temperature  to 
run  up  to  39.2-40.6°. 

From  all  these  facts  it  is  evident  that  the  most  virulent 
products  of  bacterial  metabolism  are  either  proteids  or  sub- 
stances which  have  solubilities  similar  to  those  of  the  proteids, 
and  hence  are  precipitated  with  them.  Most  authors  who  have 
worked  on  this  subject  adopt  the  former  view,  and  therefore 
call  these  poisonous  substances  toxalbumins. 

1 S.  Kitasato,  Zeitschr.  f.  Hygiene,  vol.  x.  p.  296 :  1891. 

2  Loc.  cit. 

^E.  Koch,  Deutsch,  med.  Wochenschr.,  No.  3,  and  No.  43:  1891.  Martin 
Hahn  (Nencki's  Laboratory),  Berl.  klin.  Wochemchr.,  No.  30:  1891.  The 
earlier  work  on  tubercle  toxin  is  here  quoted.  Compare  M.  C.  Helman,  Arch, 
d.  sciences  biol.,  publ.  par  I'Institut  imp.  de  Med.  exp.  ä  St.  Petersbourg,  vol.  i. 
p.  139:  1892.  O.  Bujwid,  idem,  p.  213,  and  W.  Kühne,  Zeitschr.  f.  Biol.,  vol. 
xxix.  p.  24 :  1892,  and  vol.  xxx.  p.  221 :  1893. 

*N.  Sieber,  Arch.  d.  sciences  biol.,  vol.  i.  p.  285:  1892. 


416  LECTUEE   XXVII 

The  toxalbumins  are  not  exclusively  confined  to  bacterial 
products,  but  have  been  also  found  to  exist  in  the  animal  and 
vegetable  kingdoms.  Thus  all  recent  workers^  on  the  poisonous 
secretion  of  snakes  have  come  to  the  conclusion  that  the  active 
toxic  principles  belong  to  the  group  of  proteids.  The  poison 
contained  in  the  blood-serum  of  the  muranids  is  shown  by 
Mosso  ^  to  be  of  the  same  nature  as  snake-poison.  This  author 
considers  that  this  substance  is  probably  a  proteid,  an  opinion 
likewise  held  by  Kobert  concerning  the  poison  of  spiders.^  The 
large  spider,  Lathrodectes  tredecimguttatus,  which  occurs  in  the 
south  of  Russia,  contains  poison  in  all  parts  of  its  body,  even  in 
its  legs  and  undeveloped  eggs.  If  this  poison  be  introduced 
directly  into  the  blood,  its  effect  is  more  potent  than  strychnin 
or  hydrocyanic  acid,  although  it  has  no  action  in  the  stomach, 
and  is  destroyed  on  boiling. 

The  toxalbumins  again  are  distributed  over  the  vegetable 
kingdom.  To  this  class  apparently  belong  the  intensely  poi- 
sonous constituents  of  the  jequirity  seed*  {Abrus  precatorius), 
and  that  of  Ricinus  communis^  as  well  as  the  poison  of  a 
fungus,  the  Amanita  phalloides,^  all  of  which  resemble  the 
toxalbumins  in  their  chemical  and  physical  behavior.  If 
injected  intravenously,  0.5  mg.  per  kilo,  bodyweight  is  suf- 
ficent  to  cause  death  in  the  case  of  the  poisonous  principle  of 
the  Amanita  phalloides,  and  0.01-0.02  in  the  case  of  that  of  the 
jequirity  seed.'^ 

As  the  toxalbumins  and  the  hydrolytic  ferments,  the  so- 
called  enzymes,  present  the  same  conditions  of  solubility, 
besides  possessing  many  other  chemical  qualities  in  common, 

1  R.  Norris  Wolfenden,  Journ.  of  Physiol.,  vol.  vii.  pp.  327  and  357 :  1886. 
S.  "Weir  Mitchell  and  Edward  Reichert,  "Researches  upon  the  Venoms  of 
Poisonous  Serpents."  Smithsonian  Contributions  to  Knowledge,  647,  p.  186: 
Washington,  1886.  Brieger  and  Fränkel,  Bcrl.  klin.  Wochenschr.,  Jahrg.  27, 
p.  271 :  1890. 

2  A.  Mosso,  Acad,  dei  Lincei,  vol.  iv.  p.  665  :  1885 ;  and  Arch.  f.  exper.  Path. 
u.  Pharm.,  vol.  xxv.  p.  Ill :  1889.  U.  Mosso,  Eendiconti  delta  r.  Acad,  dei 
Lincei,  p.  804:  1889. 

^  Kobert,  Sitzungsher.  d.  Naturforscher- Gesellsch.  zu  Dorpat,  vol.  viii.  pp. 
362  and  440:  1889. 

■*  Sidney  Martin  and  R.  Norris  Wolfenden,  Proc.  Roy.  Soc,  London,  vol. 
xlvi.  pp.  94  and  100:  1889.  Sophie  Glinka,  "  Beitr.  z.  Kenntniss  d.  giftigen 
Princips  d.  Jequiritysamen,"  Diss.,  Bern. :  1891.  The  earlier  literature  is  here 
quoted.  Nencki,  Schweizer  Wochenschr.  f.  Pharmacie,  No.  29 :  1891.  Reprint, 
p.  5,  Heinr.  Hellin,  "Der  giftige  Eisweisskörper  Abrin.,"  Diss.,  Dorpat:  1891. 
P.  Ehrlich,  Deutsch,  med.  Wochenschr.,  No.  44:  1891. 

5  H.  Stillmark,  "  Ueber  Ricin,"  Diss.,  Dorpat:  1888.  P.  Ehrlich,  Deutsch, 
raed.  Wochenschr.,  No.  32  :  1891. 

8  Kobert,  Sitzungsher.  d.  Nat.  Ges.  zu  Dorpat,  vol.  ix.  p.  541  et  seq. :  1891. 
This  author  gives  a  summary  of  our  present  knowledge  concerning  the  various 
poisons  in  the  different  fungi. 

'  Kobert,  idem,  vol.  ix.  pp.  116  and  553  :  1891. 


INFECTION  417 

it  was  fair  to  assume  that  they  also  shared  the  same  poisonous 
properties.  Roussy  ^  found  that  intravenous  injection  of  in- 
vertin  in  dogs  gave  rise  to  fever,  less  than  ^  rag.  to  1  kilo,  body- 
weight  being  sufficient  to  cause  a  rise  of  temperature  to  42°  C. 
H.  Hildebrandt  ^  showed  that  the  subcutaneous  injection  of 
larger  quantities  (0.1  g.)  of  pepsin,  invertin,  diastase,  was  fatal 
to  medium-sized  rabbits,  the  animals  succumbing  in  2  to  4 
days.  After  doses  of  between  0.05  and  0.1  g.  the  animals  did 
not  die  until  after  the  lapse  of  one  or  more  weeks.  With 
emulsin  and  my  rosin  a  dose  of  0.05  g.  was  always  fatal  in  2 
to  4  days.  In  dogs  relatively  larger  amounts  of  pepsin  and 
invertin  (0.1  to  0.2  g.  per  kilo.)  were  required  to  cause  death. 
In  all  the  experiments  there  was  a  rise  of  temperature  amount- 
ing on  the  average  to  2°  C. 

We  might  now  ask  :  If  the  hydrolytic  ferments  have  a 
toxic  action,  might  not  the  toxalbumins  have  an  hydrolytic 
action,  and  perhaps  by  this  very  means  develop  their  poisonous 
properties  in  the  tissues?  This  does  not  however  appear  to 
be  the  case.  Direct  experiment  has  shown  that  the  diphtheria 
and  tetanus  toxins  do  not  act  hydrolytically.^ 

It  has  frequently  been  stated  that  certain  products  of 
artificial  proteid  digestion,  certain  peptones  and  their  pre- 
cursors, the  so-called  albumoses,  have  a  poisonous  action.* 
This  action  is  only  produced  on  direct  introduction  of  these 
substances  into  the  blood,  probably  for  the  reason  that  in  the 
passage  through  the  intestinal  wall  the  peptones  are  recon- 
verted into  proteids.  But  even  in  the  former  case  the  toxic 
effects  —  narcosis  and  lowering  of  the  blood-pressure  —  are  only 
brought  about  by  very  large  doses  —  0.3  g.  per  kilo,  body- 
weight.  The  poison  is  therefore  not  of  a  violent  nature.  It 
is  possible  that  both  with  these  digestive  products  of  the 
proteids  as  well  as  with  the  enzymes,  the  toxic  effect  is  to  be 
ascribed  to  an  admixture  of  toxalbumins  arising  from  bac- 
terial metabolism.  It  is  highly  desirable  that  the  experiments 
should  be  repeated  with  absolutely  sterilized  material  under 
strict  antiseptic  precautions. 

In  the  foregoing  remarks  we  have  enumerated  the  various 

^  Roussy,  Gaz.  des  Hop.,  No.  19  and  No.  31 :  1891.  Compare  the  appreciation 
of  this  work  presented  to  the  Acad,  by  Schiitzenberger,  Gautier,  and  Hayem : 
Bull.  d.  I'Acad.  de  3Ied.,  Serie  3,  vol.  xxii.  p.  468 :  1889. 

2  H.  Hildebrandt,  Virchotv's  Arch.,  vol.  cxxi.  p.  1 :  1890. 

*  L.  Vaillard  and  H.  Vincent,  Annates  d.  V Institut  Pasteur,  Ann.  5,  p.  20  : 
1891. 

4  Schmidt-Mülheim,  Du  Bois'  Arch.,  pp.  50-54 :  1880.  Fano,  idem,  p.  277  : 
1881.  W.  Kühne  and  Pollitzer,  Verhandl.  d.  nat.-med.  Vereins  zu  Heidelberg^ 
N.  F.,  vol.  iii.  p.  292 :  1886.  R.  Neumeister,  Zeitschr.  f.  Biol.,  N.  F.,  vol.  vi.  p. 
284 :  1888. 

27 


418  LECTURE    XXVII 

properties  which  the  toxalbumins  and  the  enzymes  have  in 
common.  There  are  however  differences  not  only  between 
the  toxalbumins  and  the  enzymes  but  among  the  toxalbumins 
themselves.  A  few  of  the  latter  are,  like  the  globulins, 
insoluble  in  water,  as  for  instance  the  poisonous  proteid 
precipitates  obtained  from  cultures  of  typhus  bacilli  and 
staphylococcus  pyogenes  aureus.  Most  of  the  toxalbumins 
however  are,  like  £he  ferments,  soluble  in  water,  but  not 
dialyzable.  An  exception  to  this  is  formed  by  the  poison  of 
the  rattlesnake,^  as  well  as  of  the  tubercle  bacillus,  both  of 
which  are  dialyzable.  Tetanus  and  diphtheria  poisons  dialyze 
slowly. 

A  temperature  of  over  50°  C.  causes  many  of  the  solu- 
tions of  toxalbumin  to  lose  their  virulence ;  but  there  are 
some  which  will  stand  heating  to  60°  and  higher,  or 
even  for  a  short  time  to  100°  C,  as  for  instance  the 
poison  of  the  Indian  cobra  and  the  toxalbumin  of  the  tuber- 
cle bacillus.  We  may  assume  perhaps  that  the  toxalbumins 
which  are  rendered  innocuous  by  boiling  belong  to  the  pro- 
teids  properly  so-called,  whereas  those  which  are  not  aifected 
by  this  temperature  may  be  referred  to  the  peptons.^  If  this 
assumption  be  correct,  we  should  expect  to  find  that  the  tox- 
albumins which  are  not  affected  by  boiling  are  dialyzable. 
This  is  the  case  with  tubercle.  When  in  a  dry  condition  the 
toxalbumins,  like  the  ferments,  can  be  raised  to  a  high  tem- 
perature (e.  g.,  certain  snake  poisons  to  115°  C.)  without  losing 
their  virulence. 

Absolute  alcohol  has  no  effect  on  some  of  the  toxalbumins, 
e.  g.,  the  snake-poison,  but  others  again  it  gradually  renders 
ineffective.  Thus,  according  to  Kitasato,  the  tetanus  poison 
loses  its  power  if  it  be  exposed  to  the  action  of  70  per  cent, 
ethyl  alcohol  for  one  hour  or  to  that  of  60  per  cent,  for  twenty- 
four  hours. 

Alkalies  and  acids  weaken  or  destroy  the  operation  of 
many  toxalbumins.  The  poisonous  effect  of  snake-venom  is 
diminished  by  alkalies.  Tetanus  poison  is  destroyed  by  free 
alkalies :  a  0.3  per  cent,  solution  of  sodium  hydrate,  or  a  3.7 
per  cent,  solution  of  sodium  carbonate  will  accomplish  this  in  an 
hour  ;  a  1  per  cent,  solution  of  ammonia  must  be  allowed  twenty- 
four  hours.  Again,  a  solution  of  0.365  per  cent,  hydrochloric 
acid  will  take  twenty-four  hours,  and  one  of  0.55  per  cent,  one 
hour  to  destroy  the  tetanus  poison.     The  toxin  of  muranids  is 

^  W.  Heidenschild,  "  Unt  üb.  d.  Wirkung  d.  Giftes  d.  Brillen-  u.  Klapper- 
schlange," Diss.,  Dorpat :  1886. 

2  S.  Weir  Mitchell  and  E.  T.  Reichert,  loc.  cit. 


INFECTION  419 

deprived  of  its  activity  by  the  action  of  acetic  or  hydrochloric 
acid,  or  by  that  of  gastric  juice.  If  however  the  poisonous 
serum  be  injected  through  the  abdominal  wall  into  the  small 
intestine,  death  ensues.  I  mentioned  above  that  the  poison  of 
spiders  as  well  as  the  tubercle  and  tetanus  toxins  were  innocuous 
when  introduced  into  the  stomach. 

Before  leaving  the  consideration  of  the  toxalbumins,  I 
must  mention  one  observation  which  may  perhaps  have  a  very 
wide  bearing.  Of  late  years  many  communications  have  been 
made  concerning  the  existence  in  normal  blood  of  proteids 
which  behave  towards  certain  bacteria  like  toxalbumins.  An 
attempt  has  been  made  to  explain  the  phenomena  of  immunity 
in  this  way,  but  the  data  are  not  yet  sufficiently  precise  to  per- 
mit of  a  connected  account.^ 

1  For  a  summary  of  the  literature  on  this  subject  see  R.  Stern,  Zeitschr.  f. 
Hin.  lied.,  vol.  xviii.  p.  46:  1891.  Compare  also  the  Address  given  at  the  11th 
Congress  for  Clinical  Medicine  at  Leipzig  by  H.  Büchner,  and  printed  in  the 
JBerl.  klin.  Wochenschr.,  No.  19  :  1892  :  and  H.  Büchner,  Arch.f,  Hygiene,  vol. 
xvii.  pp.  112,  138:  1893;  G.  Tizzoni  u.  J.  Cattani,  Berl.  klin.  Wochenschr., 
Nos.  49-52:  1893;  and  Nos.  3:  1894;  M.  Hahn,  "Ueb.  d.  Beziehungen  d. 
Leukocyten  z.  bactericiden  Wirkung  d.  Blutes,"  Pro  venia  legendi,  München  : 
1895. 


LECTURE   XXVIII 


FEVER 

Almost  all  forms  of  infection  lead  to  the  complex  of  symp- 
toms which  we  term  fever.  Of  these  symptoms  the  rise  of 
temperature  is,  as  we  know,  the  most  readily  measured  and  has 
therefore  been  the  subject  of  the  most  thorough  investigation. 
Teleologically  this  rise  of  temperature  may  be  explained  on  the 
assumption  that  by  its  means  the  pathogenic  microorganisms 
are  killed,  or  at  least  arrested  in  their  development,  and  their 
pathogenic  properties  weakened. 

Thus  Heydenreich  ^  observed  that  the  spirilla  of  recurrent 
fever  lost  their  mobility  much  more  readily  at  40°  C.  than  at 
70°  C.  According  to  R.  Koch  ^  the  most  favorable  tempera- 
ture for  the  tubercle  bacillus  lies  between  37°  and  38°  C.  When 
kept  at  42°  C.  for  three  weeks,  its  further  development  is 
impeded.  For  the  gonococcus-Neisser  the  optimum  tempera- 
ture is  between  33°  and  37  C.^  A  temperature  of  39°  C.  kills 
it  in  twenty-four  hours,  and  one  of  42°  in  twelve  hours.*  De 
Simone^  found  that  the  multiplication  of  the  streptococcus 
erysipelatosus  stopped  entirely  at  39°  to  40°  C,  and  that  the 
organism  died  at  39.5°  to  41  °  C  Bard  and  Aubert  ^  found  that 
of  the  medley  of  bacteria  in  the  feces,  all  of  them  disappeared, 
with  the  exception  of  the  bacillus  coli  communis,  under  the 
prolonged  action  of  fever  temperature.  According  to  Fränkel  "^ 
the  virulence  of  the  septicemic  cocci  of  the  sputum  is  entirely 
abolished  by  growing  it  for  two  days  at  42°  C,  or  for  four  to 
five  days  at  41°  C.     Pasteur^  discovered  that  anthrax  bacilli, 

*  Heydenreich,  Centralbl.  f.  d.  med.  Wissensch.,  No.  28:  1876. 

*R.  Koch,  "Zur  Aetiologie  der  Tuberculose,"  illfrWÄ.   a.  d.   kais.  Gesund- 
keitsamte,  vol.  ii.:  1894. 

*  Bumm,  "  Der  Micro-organismus  d.  gonorrhoischen  Schleimhauterkrankung 
Gonococcus-Neisser,"  Wiesbaden:  1887. 

*  Finger,  Verh.  d.  deutsch.  Dermatolog.  Ges.,  IV.  Congress,  p.  181 :  1894. 
6  Fr.  de  Simone,  II  Morgagni,  Nos.  8-12  :  1885. 

«L.  Bard  and  P.  Aubert,  Gaz.  hebdom.  d.  Mid.  et  de  Chirurg.,  No.  35,  p. 
418  :  1891. 

'A.  Fränkel,  Zeitschr.f.  Hin.  Med.,  vol.  x.  Hft.  5  and  6  :  1886. 

*  Pasteur  in  collaboration  with  Chamberlain  and  Roux,  Comptes  rend.,  vol. 
xcii.  pp.   422,  662,  666,  and   1379:  1881.     Compare   R.    Koch,  "Zur  Aetiol.   d. 

420 


FEVER  421 

after  being  exposed  for  some  time  to  a  temperature  of  42°  to 
43°  C,  lost  their  pathogenic  character,  and  that  animals  when 
inoculated  with  the  bacilli  in  this  condition  became  immune 
to  the  actual  disease.  G.  and  F.  Klemperer^  heated  broth-cul- 
tures of  pneumococci  for  two  to  three  days  to  41°  to  42°  C, 
and  found  that  when  they  were  injected  into  rabbits  the  latter 
were  rendered  immune  to  the  infection  of  pneumococci. 

These  results  not  only  explain  the  significance  of  fever 
but  also  indicate  how  immunity  may  occur  after  infectious 
diseases.  In  this  connection  we  must  remember  that  in  fever 
the  average  temperatures  only  are  taken,  and  it  is  quite  possible 
that  in  certain  tissues,  and  perhaps  more  esjsecially  in  those 
parts  where  the  bacteria  most  abound,  the  temperature  runs 
up  to  a  much  higher  level.  The  rise  of  temperature  in  fever 
would  therefore  be  one  of  the  processes  of  self-protection  and 
self-regulation,  of  which  we  have  so  many  examples  in  the 
body.^  This  view  concerning  the  significance  of  fever  tempera- 
tures is  not  contradicted  by  the  fact  that  some  of  the  pathogenic 
organisms  are  able  to  withstand  considerable  rise  of  temperature. 
For  instance  the  temperature  of  42  °  C.  does  not  kill  the  typhoid 
bacillus,  and  only  slightly  impedes  its  rate  of  propagation. 
The  typhoid  bacilli  must  be  exposed  to  a  temperature  of  about 
44.5°  C.  for  a  considerable  time  before  any  appreciable  number 
are  killed.^ 

With  regard  to  the  mechanism  by  which  the  rise  of  tem- 
perature is  brought  about,  it  was  first  considered  that  it  was  prob- 
ably due  to  an  increased  metabolism.  Alfred  Vogel,  *  adopting 
Liebig's  titration  method  in  1854,  found  that  the  nitrogenous 
excretion  was  augmented  in  cases  of  febrile  diseases.      This 


Milzbrandes,"  Mitth.  a.  d.  kais.  Gesundheitsamt.,  vol.  i. :  1881 ;  and  Arloing, 
"  Les  virus,"  Paris  :  1896. 

^  G.  and  F.  Klemperer,  Berl.  klin  Wochenschr.,  Nos.  34  and  35  :  1891. 

^  If  this  interpretation  of  the  significance  of  fever  be  correct,  the  treatment 
of  febrile  disorders  by  means  of  cold  baths  and  antipyretic  remedies  would  appear 
to  be  a  bad  one.  For  information  on  these  debated  questions  the  following 
articles  may  be  recommended  :  Unverricht,  Deutsch,  med.  Wochenschr.,  Jahrg, 
13,  pp.  452  and  478 :  1887 ;  and  Jahrg.  14,  pp.  749  and  778 :  188 ;  Liebermei- 
ster, idem,  vol.  xiv.  pp.  1  and  26 :  1888 ;  Naunyn,  Arch.  f.  exper.  Path.  u.  Pharm.. 
vol.  xviii.  p.  49 :  1884;  Arnaldo  Cantani,  "Ueb.Antipyrese,"  Vortrag,  Verhandl. 
d.  X.  internat.  med.  Congresses,  Berlin,  Hirschwald,  p.  152 :  1891.  A  critical 
account  of  the  literature  on  the  action  of  the  antipyretic  remedies  is  given  by 
Gottlieb,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xxvi.  p.  419:  1890;  vol.  xxviii. 
p.  167 :  1891.  Compare  also  A.  Loewy  and  P.  F.  Richter,  Deutsch,  med.  Woch- 
enschr.,  No.  15,  p.  240 :  1895  ;  and  Virchow's  Arch.,  vol.  cxlv.  p.  49 :  1896. 

'Max  Müller,  "Ueb.  d.  Einfl.  v.  Fiebertemp.  a.  d.  Wachsthumgeschwind- 
igkeit  u.  d.  Virulenz  d.  Typhus  bacillus,"  Diss.,  Breslau:  1895;  reprinted  from 
the  Zeitschr.  f.  Hygiene  u.  Infectionskrankheiten,  vol.  xx. 

^A.  Vogel,  Zeitschr.  f.  ration.  Med.,  N.F.,  vol.  iv.  p.  362:  1854;  and  "Klin- 
ische Unt.  Ü.  d.  Typhus,"  Erlangen  :  1860. 


422  LECTURE    XXVIII 

statement  was  subsequently  confirmed  by  many  observers.^  At 
the  same  time  elimination  of  the  sulphuric  acid  is  correspond- 
ingly increased,  as  might  have  been  expected.^ 

Liebermeister  ^  and  Ley  den*  found  that  the  output  of  COj 
was  also  increased  in  fever.  These  observations  on  man  were 
confirmed  by  experiments  on  animals  carried  out  by  different 
observers/  and  it  was  moreover  ascertained  that  an  increased 
amount  of  oxygen  was  taken  in  as  well  as  a  larger  amount  of 
carbonic  acid  eliminated.^ 

It  is  however  doubtful  whether  this  heightened  metabolism 
is  the  cause  of  the  rise  in  temperature.  In  the  first  place,  we 
know  that  in  a  normal  person  a  very  considerable  increase  in 
metabolism  may  occur  (e.  g.,  in  strenuous  muscular  work)  with- 
out any  rise  of  temperature,  since  the  body  possesses  various 
means  of  compensating  for  the  increased  heat  production  by 
increasing  the  heat  loss.  In  the  second  place,  the  metabolism 
is  not  quickened  in  all  fevers.  Numerous  experiments  on  man 
and  on  animals  have  shown  that  in  some  cases  of  fever  the 
intake  of  oxygen  and  the  output  of  carbonic  acid  remains  the 
same  or  is  even  less  than  normal.'' 

The  rise  of  temperature  must  therefore  have  some  other 
cause  than  merely  the  increase  of  metabolism.  There  is  only 
one  other  theory  left,  i.  e.,  that  there  is  less  heat  given  off. 
This  idea  was  warmly  supported  by  L.  Traube,^  who  taught  that 

^  An  account  of  the  comprehensive  literature  is  given  by  Senator,  "  Unt.  üb. 
d.  fieberhaften  Process,"  Berlin,  1873,  p.  94  et  seq.;  and  by  Naunyn,  Arch.  f. 
exper.  Path.  u.  Pharm.,  vol.  xxviii.  p.  49  :  1884.  Compare  also  L.  Riess,  Virchow's 
Arch.,  vol.  xiii.  p.  127 :  1886  ;  Hirschfeld,  Berl.  klin.  Wochenschr.,  No.  2 :  1891 ; 
G.  Klemperer,  Deutsch,  med.  Wochenschr.,  No.  15 :  1891. 

-  Fiirbringer,  Virchow's  Arch.,  vol.  Ixxiii.  p.  39 :  1878. 

^  Liebermeister,  Deutsch.  Arch.  f.  Hin.  Med.,  vol.  vii.  p.  75  :  1870 ;  and  vol. 
viii.  p.  153:  1871;  "Handbuch  d.  Patholog.  u.  Therapie  d.  Fiebers,"  Leipzig: 
Vogel,  1875. 

*Leyden,  Deutsch.  Arch.  f.  klin.  Med.,  vol.  v.  p.  237:  1869;  and  vol.  vii. 
p.  536:  1870.     Centralbl.  f.  d.  Med.  Wissensch.,  No.  13:  1870. 

s  Silujanoff,  Virchow's  Arch.,  vol.  liii.  p.  327  :  1871 ;  A.  Fränkel,  Verhandl. 
d.  physiolog.  Gesellsch.  z.  Berlin,  4th  Feb.  1894;  E.  Leyden  and  A.  Fränkel, 
Centralbl.  f.  d.  med.  Wissensch.,  p.  706:  1878;  Virchow's  Arch.,  vol.  Ixxvi.  p. 
136:  1879. 

®  Colasanti,  Pflilger's  Arch.,  vol.  xiv.  p.  125  :  1876  ;  D.  Finkler,  idem,  vol. 
ixix.  p.  89 :  1887  ;  A.  Lilienfeld,  idem,  vol.  xxxii.  pp.  293-356 :  1883. 

'  Senator,  Virchow's  Arch.,  vol.  xlv.  p.  351 :  1869.  "  Unt.  üb.  d.  fieberhaften 
Process  u.  seine  Behandl.,"  Berlin,  Hirschwald,  1873.  Du  Bois'  Arch.,  p.  1 : 
1872;  'W^rth^im,  Deutsch.  Arch.  f.  klin.  Med.,  vol.  xv.  p.  173:  1875.  Wiener 
med.  Wochenschr.,  Nos.  3-7,  1876 ;  Nos.  32,  34  and  35,  1878.  Fr.  Kraus,  Zeitschr. 
f.  klin.  Med.,  vol.  xviii.  p.  160 :  1891.  A.  Loewy,  Virchow's  Arch.,  vol.  cxxvi. 
p.  218 :  1891. 

*  L.  Traube,  Allgem.  med.  C'entralzeitung,  July  1,  July  8  and  Dec.  22,  1863, 
and  March  23,  1864.  "  Ges.  Beiträge  z.  Patholog.  u.  Physiolog.,"  Berlin,  Hirsch- 
wald,  vol.  ii.  pp.  637  and  679  :  1871.  A  list  of  the  numerous  authors  who  prior 
to  Traube  have  put  forward  the  theory  of  diminished  heat  loss  in  fever,  although 


TEVER  423 

in  fever  a  constriction  of  the  peripheral  blood-vessels  occurred 
with  diminished  flow  of  blood  to  the  skin,  so  that  there  was 
diminished  heat  loss,  accompanied  by  congestion  in  the  interior 
of  the  body.  By  means  of  Mosso's  Plethysmograph,  Maragliano 
showed  that  in  various  febrile  diseases  the  cutaneous  vessels 
contracted,  and  moreover  that  they  commenced  doing  so  be- 
fore the  rise  of  temperature  was  perceptible.  As  contraction 
continued,  the  temperature  began  to  rise,  both  reaching  the 
maximum  at  the  same  time.  An  expansion  of  the  blood-vessels 
preceded  the  fall  in  temperature,  which  came  down  to  normal 
while  the  blood-vessels  were  still  maximally  dilated.^ 

The  diminished  loss  of  heat,  especially  in  the  first  stages  of 
fever,  has,  with  the  help  of  the  calorimeter,  been  proved  by 
many  observers  from  direct  experiments  on  man  and  animals.^ 

Many  unsuccessful  attempts  have  been  made  to  decide  ex- 
perimentally what  part  the  nervous  system  takes  in  the  increased 
metabolism  and  the  diminished  loss  of  heat.  Numerous  ex- 
periments on  animals  have  shown  that  by  mechanical  injury  or 
electrical  stimulation  of  certain  parts  of  the  brain  —  e.  g.,  the 
median  portion  of  the  corpus  striatum,  &c.,  a  lasting  rise  of 
temperature  may  be  induced,  accompanied  by  increased  metab- 
olism. But  this  is  a  different  process  from  that  involved  in 
fever,  since  there  is  neither  contraction  of  the  blood-vessels  nor 
diminished  loss  of  heat.^ 

Of  the  two  factors  which  bring  about  a  rise  of  temperature 
in  fever,  i.  e.,  the  increased  production  of  heat  by  more  rapid 
metabolism  and  the  diminished  loss  of  heat,  the  latter  is 
certainly  the  more  important,  since,  as  I  have  already  men- 
tioned, a  febrile  condition  may  occur  in  the  absence  of  the  first 
factor.  Some  authors  indeed  have  gone  so  far  as  to  regard 
the  first  factor,  increased  metabolism,  as  the  consequence  and 


perhaps  not  in  so  clear  and  decisive  a  manner,  will  be  found  in  Maragliano, 
Zeitschr.  f.  klin.  Med.,  vol.  xiv.  p.  309  :  1888,  where  a  careful  notice  of  the 
literature  on  the  subject  is  also  given. 

'  Maragliano,  loc.  cit.,  pp.  316-319. 

*  Senator,  "  Unt  üb.  d.  fieberhaften  Process  u.  seine  Behandlung."  Berlin, 
Hirschwald,  1873.  Carl  Rosenthal,  Du  Bois'  Arch.,  p.  1  :  1888.  J.  Rosenthal, 
Berlin,  klin.  Wochenschr.,  p.  785:  1891,  and  "Internat.  Beiträge  z.  wissen- 
schaftl.  Med.,"  Festschrit.,  R.  Virchow  gewidmet.  Berlin,  Hirschwald,  vol.  i. 
p.  413  :  1891. 

^  Further  discussion  of  these  experiments  would  be  beyond  the  scope  of  this 
text-book.  For  further  references  I  will  mention  :  J.  Ott,  Journ.  of  Nervous 
and  Mental  Diseases,  1884,  and  Therapeutic  Gazette,  Sept.  15,  1887  ;  The  Medical 
News,  Dec.  10,  1887;  Aronsohn  and  Sachs,  Pflüger' s  Arch.,  vol.  xxxvii.  p.  232  : 
1885;  H.  Girard,  Arch,  de  Physiol.,  Serie  III.  vol.  viii.  p.  281 :  1886  :  and  Serie 
IV.,  vol.  i.  pp.  312,  463  :  1888  ;  Hale  White,  Journ.  Physiol.,  vol.  ii.  Nos.  1  and  2 
1890  ;  Ugolino  Mosso,  Arch.  f.  exper.  Path.  u.  Pharmakol.,  vol.  xxvi.  p.  316  : 
1890. 


424  LECTURE    XXVIII 

not  as  the  cause  of  the  rise  in  temperature,  since  direct 
experiments  on  animals  and  on  man  have  sho"\vn  ithat,  if  the 
temperature  be  artificially  raised  and  the  loss  of  heat  be  at  the 
same  time  prevented  by  warm  baths,  the  excretion  of  urea  is 
increased.^ 

It  is  however  very  doubtful  whether  this  increase  in  urea 
observed  with  an  artificial  rise  of  temperature  is  a  sufficient 
explanation  of  the  large  quantity  of  additional  urea  eliminated 
in  fever.  The  increase  of  urea  brought  about  by  artificial 
means  was  always  much  less  than  that  in  fever,  and,  in  fact, 
in  some  experiments  it  did  not  occur  at  all."  Moreover  the 
theory  that  increased  metabolism  is  due  to  the  rise  of  tem- 
perature is  belied  by  the  fact  that  the  increased  nitrogenous 
excretion  in  fever  does  not  run  parallel  with  the  heightened 
temperature,  but  usually  reaches  its  maximum  after  the  crisis.^ 
In  many  cases  the  rise  of  temperature  is  only  slight  during  the 
febrile  stage,  and  yet  there  is  a  large  increase  in  the  urea 
excretion  after  the  fever  has  abated.  In  one  case  of  recurrent 
fever  47.8  g.  of  urea  were  excreted  on  the  second  day  after  the 
crisis,*  in  a  case  of  typhus  exanthematicus  160  g.  of  urea  on  the 
third  and  fourth  days  after  the  temperature  had  fallen.^  Occa- 
sionally in  diseases  dae  to  infection  the  proteid  disintegation  may 
even  precede  the  rise  of  temperature.*'  Schimauski  ^  showed  that, 
if  pus  was  injected  into  fowls,  there  was  frequently  no  alteration 
in  temperature,  although  a  large  additional  amount  of  nitrogen 
was  excreted.  LilienfekP  found  that  after  pyogenic  injec- 
tions an  increase  in  the  intake  of  oxygen  and  output  of  carbonic 
acid  occurred,  even  when  the  rise  of  temperature  was  prevented 
by  cold  baths. 

From  these  experiments  we  see  that  the  increase  in  metab- 
olism is  not  a  consequence  of  the  rise  of  temperature.  On 
the  other  hand,  it  is  not  improbable  that  the  increased  metab- 
olism— especially  in  the  later  stages  of  the  febrile  process — may 

■!  Bartels,  Griefswalder  med.  Beitr.,  vol.  iii.  p.  36 :  1865  ;  Naunyn,  Berl.  klin. 
Wochenschr.,  p.  42  :  1869  ;  Du  Bois'  Arch.,  p.  159  :  ,1870  ;  Schleich,  Arch, 
f.  exper.  Path.  u.  Pharm.,  vol.  iv.  p.  82  :  1875  ;  P.  Pächter,  Virchow's 
Arch.,  vol.  cxxiii.  p.  118 :  1891 ;  R.  Topp,  Therapeut.  Ifonatshefte,  pp.  1,  55 : 
1894. 

2  C.  F.  A.  Koch,  Zeitschr.  f.  Biol.,  vol.  xix.  p.  447  :  1883  ;  N.  P.  Simanow- 
sky,  Zeitschr. f.  Biol.,  vol.  xxi.  p.  1  :  1885. 

3  Anderson,  Edinh.  Med.  Journ.,  p.  708  :  Feb.  1866.  Compare  Wood  and 
Marshall,  Journ.  of  Nerv,  and  Meat.  Diseases,   No.  1  :  1891. 

•*  A.  Pribram  and  J.  ßcbitschek,  Prag  Vierteljahr sschr.,  vol.  civ.  p.  318  : 
1869. 

^  Naunyn,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xviii.  p.  83  :  1884. 
^  Sydney  Pi,inger,  Lancet,  Aug.  6,  1859. 

'  Schimauski,  Zeitschr.  f.  physiol.  Chem.,  vol.  iii.  p.  396  :  1879. 
«  A.  Lilienfeld,  Pfläger's  Arch.,  vol.  xxxii.  p.  293  :  1883. 


FEVER  425 

be  partly  referred  to  the  death  of  the  aifected  tissues,  which  must 
be  got  rid  of  when  they  have  undergone  disintegration.  This 
death  of  individual  tissue-elements  may  be  traced  by  direct 
anatomical  observation.^ 

The  red  blood-corpuscles  are  among  the  elements  which  are 
destroyed  in  this  way,  as  evidenced  by  the  production  of  a  larger 
amount  of  urobilin.^  (Compare  pp.  323,  339.)  The  leuco- 
cytes, on  the  other  hand,  are  usually  augmented  in  most  of  the 
zymotic  diseases,  as  in  the  case  of  many  other  disturbances, 
which  are  connected  with  increased  disintegration  of  the  tissues. 
It  appears  that  the  object  of  the  multiplication  of  the  leucocytes 
is  to  render  the  waste-products  harmless.  Direct  experiments 
have  shown  that  the  number  of  leucocytes  rises  on  the  introduc- 
tion of  foreign  substances  of  the  most  varied  nature  into  the 
body.^ 

There  is  probably  a  connection  between  the  increased  dis- 
integration of  proteid  and  the  occurrence  of  organic  acids  — 
volatile  fatty  acids*  and  lactic  acid^ — as  well  as  the  diminution 
of  the  alkalescence  of  and  the  carbonic  acid  in  the  blood,  and 
the  passage  of  aceton,  aceto-acetic  acid,  oxybutyric  acid,^  and 
volatile  fatty  acids '^  into  the  urine.  (Compare  pp.  391,  392.) 
The  amount  of  carbonic  acid  in  the  arterial  blood  may  sink  to 
10.7  vol.  per  cent.®  The  increased  elimination  of  ammonia  in 
fever  (which  may  rise  to  as  much  as  2.7  g.  per  diem^)  may  be 
connected  with  the  increased  formation  of  these  organic  acids. 
(Compare  pp.  292,  404.)  The  appearance  of  acids  in  the  blood, 
the  diminution  of  the  alkalescence  and  of  the  carbonic  acid  have 
been  likewise  observed  as  results  of  the  action  of  inorganic 

^  These  experiments  are  described  by  Liebermeister,  "  Handb.  d.  Patholog.  u- 
Therap.  d.  Fiebers.,"  chap.  iv.  p.  437,  Leipzig,  Vogel :  1875. 

2  G.  Hoppe-Seyler,  Virchow's  Arch.,  voL  cxxiv.  p.  30:  1891;  and  vol. 
cxxviii.  p.  43  :  1892.  In  the  former  volume  all  the  previous  work  on  the  occur- 
rence of  urobilin  in  disease  is  collected. 

3  An  account  of  the  complete  and  comprehensive  literature  on  the  behavior  of 
the  leucocytes  is  given  in  the  monograph  of  H.  Rieder,  "  Beitr.  z.  Kenntniss  d. 
Leukocytose,"  Leipzig,  Vogel :  1892.    Compare  also  Lecture  XV.  p.  222. 

*  von  Jaksch,  "  Klinische  Diagnostik,"  2d  edition,  p.  59  :  1889. 

^  Minkowski,  Arch.  /.  exper.  Path.  u.  Pharm.,  vol.  xix.  p.  209  :  1885. 

^  Deichmüller,  Centralbl.  f.  klin.  3Ied.,  No.  1:  1882.  Seifert,  Verhandl.  d- 
Würzburger  phys.-med.  Ges.,  vol.  xvii.  p.  93:  1883.  Liitten,  Zeitschr.  f.  klin. 
Med.,  vol.  vii.  Suppl.  p.  82:  1884.  Penzoldt,  Deutsch.  Arch.  f.  klin.  Med.,  vol. 
xxxiv.  p.  127:  1884.  v.  Jaksch,  "  Ueb.  Acetonurie  u.  Diacetonurie,"  Berlin: 
1885.    Kiilz,  Zeitschr.  f.  Biolog.,  vol.  xxiii.  p.  336  :  1887. 

■^  von  Jaksch,  Zeitschr.  f.  physiol.  Chem.,  vol.  x.  p.  536  :  1886. 

*  Jul.  Geppert,  Zeitschr.  f.  klin.  3Ied.,  vol.  ii.  p.  355 :  1881.  Compare  also 
Minkowski,  loc.  cit. 

3  Hallervorden,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xii.  p.  249  :  1880.  This 
author  also  quotes  the  earlier  work  of  Duchek  and  Koppe.  Compare  also 
Bohland,  i^üö'er's  Arch.,Yo\.  xliii.  p.  30:  1888;  and  G.  Gumlich,  ZeiYscAr. /. 
physiol.  Chem.,  vol.  xvii.  p.  30 :  1892. 


426  LECTURE    XXVIII 

poisons,  such  as  arsenic,  phosphorus,  &c. ;  ^  and  it  appears 
therefore  as  if  the  toxins,  which  are  the  metabolic  products  of 
the  pathogenic  bacteria  and  which  occasion  the  febrile  zymotic 
diseases,  involve  a  similar  disturbance  in  the  chemistry  of  the 
blood. 

Albuminuria,^  although  not  an  invariable,  is  yet  a  frequent 
accompaniment  of  high  fever.  Its  connection  with  the  other 
changes  in  the  chemistry  of  fever  is  not  yet  explained.  It 
would  be  an  obvious  assumption  that  the  kidneys,  in  endeavor- 
ing to  rid  the  organism  of  the  infective  substances  or  even  of 
the  pathogenic  microorganisms  themselves,  become  irritated  by 
these  poisons  which  thus  produce  albuminuria.  It  has  in  fact 
been  stated  that  poisonous  substances  are  to  be  found  in  the 
urine  of  febrile  patients.^  Brieger  and  Wassermann,*  in  exam- 
ining the  urine  of  a  case  of  erysipelas,  succeeded  in  isolating 
a  toxalbumin  which  had  a  poisonous  effect  on  guinea-pigs. 
The  disease  in  which  the  pathogenic  bacilli  themselves  have,  so 
far,  been  found  in  the  kidneys  are  pyemia,  anthrax,  glanders, 
diphtheria,  scarlet  fever,  erysipelas,  pneumonia,  typhoid,  and 
recurrent  fever.^  In  typhoid,  the  specific  bacteria  were  found 
by  Konjajeff  ^  occasionally  in  the  urine,  as  well  as  in  the  kid- 
neys. In  eleven  out  of  forty-eight  cases  of  the  same  malady, 
Neumann^  detected  bacilli  in  the  urine.  Karlinski^  asserts 
that  the  typhoid  bacilli  can  be  detected  far  more  readily  in  the 
urine  than  in  the  feces.  Whereas  in  the  latter  they  could  not 
be  discovered  until  the  ninth  day  of  the  disease,  they  were  fre- 
quently found  in  the  urine  as  early  as  the  third  day.  Bacilli 
were  found  in  twenty-one  out  of  forty-four  cases. 

There  is  another  change  which  often  occurs  in  the  metabol- 
ism in  febrile  diseases,  i.  e.,the  diminution,  often  very  remarkable, 
in  the  excretion  of  chlorin.     This  substance  sometimes  almost 


^Hans  Meyer  and  Fr.  Williams,  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xiii. 
p.  70:  1881.  Hans  Meyer,  idem,  vol.  xiv.  p.  313:  1882;  and  vol.  xvii.  p.  304: 
1883. 

2  The  literature  is  given  by  Senator,  "  Die  Albuminurie,"  2d  edition,  Berlin, 
Hirschwald:  1890.  Compare  also  Hiibener,  "Ueb.  Albuminurie  b.  Infections 
krankheiten,"  Diss.,  Berlin:  1892. 

3  The  following  works  may  be  selected  from  the  voluminous  literature : 
Bouchard,  "Legons  sur  les  auto-intoxications,"  Paris:  1887.  F.  Selmi,  Accad. 
d.  scienze  di  Bologna,  1879  ;  and  Ann.  di  chim.  e.  di  farm.,  vol.  viii.  p.  3 :  1888. 
Compare  also  the  discordant  results  of  E.  Bonardi,  Riv.  clinica,  p.  389 :  1890. 

*  Brieger  and  Wassermann,  Chariti-Annalen,  Jahrg.  17,  p.  834 :  1892. 
»Eibbert,  Deutsch,  med.  Wochenschr.,  No.  39,  p.  805:  1889.    This  author 

quotes  the  literature  on  this  subject. 

^Konjajeff,  Jescheniedielnaja  klinitscheskaja  Gazeta,  Nos.  33-38:  1888. 
Summarized  in  Centralhl.  f.  Bacteriolog.  u.  Parasitenkunde,  vol.  vi.  p.  672 :  1889. 

'H.  Neumann,  Berlin,  klin.  Wochenschr.,  No.  6:  1890. 

*  J.  Karlinski,  Prag.  med.  Wochenschr.,  Nos.  35  and  36  :  1890. 


FEVER  427 

entirely  disappears  from  the  urine  in  cases  of  croupous  pneu- 
monia. ^  This  symptom  is  however  merely  temporary,  and 
does  not  last  more  than  three  days  at  the  most.^  No  one  has 
yet  succeeded  in  explaining  this  phenomenon  or  of  determining 
its  connection  with  the  other  symptoms  of  fever. 

*  J.  F.  Heller,  Helleres  Arch.  f.  physiol.  u.  patholog.  Chem.  u.  Mikroskop. 
vol.  iv.  p.  523  :  1847;  Kedtenbacher,  Zeitschr.  d.  Ges.  d.  Atrzte  in  Wien.,  p.  373  : 
1850;  S.  Moos,  Zeitschr.  f.  rat.  Med.,  N.  F.,  vol.  vii.  p.  291:  1855;  E.  Unruh, 
Virchow's  Arch.,  toI.  xlviii.  p.  227  :  1869 ;  Röhmann,  Zeitschr.  f.  klin.  Med.,  vol. 
i.  p.  513:  1880;  E.  Klees  ("Over  chloorvermindering  in  de  urine,"  &c.,  Diss., 
Amsterdam :  1885)  attempts  to  show  that  the  diminished  excretion  of  chlorin  in 
acute  diseases  is  connected  with  a  disturbance  in  the  renal  function  (albu- 
minuria). 

*  C.  G.  Lehmann,  Lehr.  d.  physiol.  Chem.,  vol.  ii.  p.  392,  Leipzig :  1850. 


LECTURE   XXIX 


THE    DUCTLESS   GLANDS  :    THE    SUPRARENAL   CAPSULES,    THE 
THYROID    GLAND,    THE    PITUITARY    BODY 

There  are  three  organs  in  our  body  which  have  the  epithe- 
lial structure  of  glands,  but  are  without  ducts  :  the  suprarenal 
capsules,  the  thyroid  gland,  and  the  pituitary  body.  If  we 
would  attribute  to  these  organs  functions  similar  to  those  of 
the  glands,  we  must  assume  that  they  obtain  from  the  blood 
certain  substances  which  undergo  alteration  in  their  epithelial 
cells,  the  products  of  conversion  being  again  returned  to  the 
blood.  These  changes  must  be  of  the  greatest  importance  in 
the  vital  process,  since  extirpation  of  the  suprarenal  capsules 
as  well  as  of  the  thyroid  gland  is  followed  by  the  death  of  the 
animal  upon  which  the  experiment  is  made. 

In  consequence  of  the  well-known  discovery,  published 
in  1855  by  Addison,^  concerning  the  relation  of  bronzing 
of  the  skin  to  disease  of  the  suprarenal  capsules,  Brown- 
S^quard^  investigated  the  results  of  the  extirpation  of  these 
organs  in  animals.  He  showed  that  such  animals  as  rabbits, 
guinea-pigs,  cats,  dogs  and  mice  never  survived  the  excision  of 
both  suprarenals  for  more  than  two  days  at  the  most.  After 
the  removal  of  only  one  suprarenal  they  lived  for  a  longer  time, 
and  Brown-S^quard  considered  that  they  might  possibly  be 
kept  permanently  alive.  This  author  endeavored  by  numer- 
ous experiments  to  prove  that  death  after  excision  of  both 
suprarenal  capsules  was  not  brought  about  by  the  operative 
interference — the  animals  survived  extirpation  of  the  kidneys 
longer  than  they  did  that  of  the  organs  under  discussion — nor 
by  the  injury  done  to  the  numberless  nerve-fibers  which  run 
from  the  suprarenals  to  the  plexus  semilunaris,  but  to  the 
abolition  of  the  suprarenal  functions.  He  showed  that  if  the 
blood  of  an  animal,  which  was  dying  in  consequence  of  the 
removal  of  its  suprarenal  capsules,  were  injected  into  a  vein 

^Thos.  Addison,  "On  the  constitutional  and  local  effects  of  disease  of  the 
suprarenal  capsules"  :  London,  1855. 

^E.  Brown-Sequard,  Comjyies  rendus,  vol.  xliii.  pp.  422  and  542:  1856;  and 
vol.  xiv.  p.  1036 :  1857. 

428 


THE    DUCTLESS    GLANDS  429 

of  another  animal  in  whom  only  one  of  these  organs  had  been 
cut  out,  the  death  of  the  second  animal  was  hastened.  Again, 
if  the  blood  of  a  normal  animal  were  injected  into  a  vein  of  an 
animal,  which  was  dying  from  the  effects  of  excision  of  both 
suprarenals,  the  life  of  the  latter  was  prolonged. 

Brown-Seqnard  is  therefore  the  founder  of  the  modern 
doctrine  concerning  the  functions  of  the  ductless  glands,  i.  e., 
that  these  glands  convert  injurious  into  harmless  substances 
and  produce  the  substances  which  are  necessary  for  the  normal 
functioning  of  other  organs.  This  work  of  the  ductless  glands 
is  termed  "internal  secretion."  We  may  however  here  remark 
that,  besides  the  preparation  of  the  secretions  which  are  dis- 
charged by  the  ducts,  the  glands  properly  so  called  may  also 
be  forming  an  important  internal  secretion,  as  already  proven 
in  the  cases  of  the  pancreas  (p.  400)  and  liver  (p.  334). 

These  operations  of  Brown-S§quard  have  been  more  recently 
repeated  with  aseptic  precautions,  and  the  results  confirmed.^ 
The  animals  experimented  upon  never  survived  extirpation  of 
both  suprarenals  for  more  than  a  few  days.  A  different  result 
was  however  obtained  by  J.  Pal,^  who  succeeded  in  keeping  a 
dog  alive  for  4J  months  after  excision  of  both  suprarenals. 
Pal  controlled  his  experiments  by  an  autopsy,  thus  removing 
the  obvious  objection  that  the  excision  might  have  been  incom- 
plete. We  must  also  take  note  of  the  statement  that  rats  are 
not  affected  by  excision  of  the  suprarenals.'  In  one  of  the 
latest  researches  on  the  subject  by  Szymonowicz*  however  this 
author  declares  his  conviction  that  dogs  never  survive  the  ex- 
tirpation of  both  capsules  for  more  than  fifteen  hours  at  the 
most,  and  that  the  statements  of  previous  experimenters  to  the 
contrary  were  either  due  to  incomplete  excision  or  to  the  fact 
that  accessory  suprarenals  were  left  behind. 

Investigation  of  the  functions  of  the  suprarenal  capsules  is 
rendered  peculiarly  difficult  owing  to  the  fact  that  this  organ  is 
rich  in  sympathetic  ganglion  cells,  from  which  numerous  fibers 
pass  to  other  parts  of  the  sympathetic  nervous  system.  For 
this  reason  operations  on  the  suprarenals  cause  indirect  disturb- 
ances of  the  most  varied  nature.^ 

1  F.  and  S.  Marino-Zucco,  Atti  della  H.  Accad.  dei  Lincei,  S.  V.,  toI.  i.  p. 
122:  1894;  Riforma  med.,  vol.  i.  p.  709:  1894;  E.  Abelous  and  P.  Langlois, 
Comptes  rend.  Soc.  biol.,  vol.  xliv.  pp.  165,  388,  410,  490,  864 :  1892.  L.  Szy- 
monowicz,  Pfliiger's  Arch.,  vol.  Ixiv.  p.  97  :  1896. 

2  J.  Pal,  Wien.  klin.  Wochenschr.,  p.  899:   1894. 

3E.  Boinet,  Comp.  rend.  Soc.  biol.,  vol.  xlvii.  pp.  273,  325,  498:  1895. 

•*L.  Szymonowicz,  Pfliiger's  Arch.,  vol.  Ixiv.  p.  97  :  1896. 

5  G.  Tizzoni,  Arch.  ital.  de  Biolog.,  vol.  vii.  p.  372  :  1888.  G.  Jacoby,  Arch, 
f.  exper.  Path.  u.  Pharm.,  vol.  xxis.  p.  171 :  1891.  N.  de  Dominicis,  Arch,  de 
Physiol.,  vol.  xxvi.  p.  810 :  1895.    J.  Pal,  loc.  cit. 


430  LEcrruRE  xxix 

A  voluminous  literature  has  of  recent  years  appeared  on  the 
specific  constituents  of  the  capsules,  on  the  poisons  which  are 
stored  up  in  them/  on  the  substances,  which  the  suprarenals 
pass  on  to  the  blood  and  which  are  supposed  to  have  an  influ- 
ence on  the  innervation  of  the  blood-vessels,  heart,  and  respira- 
tory organs,^  on  the  chromogens  in  the  capsules,  which  are  con- 
sidered to  be  related  to  the  dark  pigment  that  is  deposited  in 
the  skin  in  Addison's  disease,'  etc.  But  for  the  present  it  is 
not  possible  to  give  a  short  connected  account  of  the  indefinite 
and  contradictory  statements. 

An  interesting  observation  has  been  made  on  animals,  from 
whom  only  one  capsule  had  been  removed,  viz.,  that  black 
patches  appeared  on  the  skin,*  corresponding  to  the  dark  pig- 
mentation in  patients  suifering  from  Addison's  disease. 

The  discovery  that  the  thyroid  gland  was,  like  the 
suprarenals,  indispensable  to  the  animal  economy,  was  again 
made  in  the  domains  of  pathology.  The  earlier  experiments 
and  speculations  of  the  physiologists  concerning  the  significance 
of  the  thyroid  gland  had  not  borne  any  fruit. 

In  1873  Sir  William  GulP  showed  at  the  Clinical  Society 
in  Londou  five  cases  of  a  disease  to  which  he  was  the  first  to  call 
attention,  and  which  he  termed  "  a  cretinoid  state  supervening 
in  adult  life  in  women."  In  1878  William  M.  Ord^  described 
five  other  cases  of  the  same  malady.  An  invariable  symptom 
is  present  in  the  thickening  and  swelling  of  the  skin,  which 
occurs  usually  in  the  face  but  sometimes  extends  also  to  the 
extremities  and  other  portions  of  the  body,  as  well  as  to  the 
mucous  membranes  of  the  internal  organs  This  thickening 
cannot  be  regarded  as  edema ;  if  the  swollen  skin,  be  cut,  no 
serum  flows  out.  It  is  due  to  an  active  new  formation  of  a 
connective  tissue  rich  in  mucin.  On  account  of  the  invariable 
occurrence  of  this  symptom  Ord  called  the  disease  "  myxedema." 
Other  trophic  disturbances  were  likewise  present :  dryness  of 
the  skin  in  consequence  of  insufficient  secretion  of  sweat  and 
sebum,   baldness,   atrophy  of  the  nails    and    teeth,   etc.      By 

1  P.  Foa  e  P.  Pellacani,  Arch.  p.  I.  scienze  med.,  vol.  vii.  p.  113 :  1883.  S. 
Fränkel,  Wien.  med.  Blätter,  Nos.  14,  15  and  16:  1896. 

2  G.  Oliver  and  E.  A.  Schäfer,  Proc.  Physiol.  Soc,  March  10, 1894,  and  March 
16,  1895,  L.  Szynionowicz,  loc.  dt. 

3  Vulpian,  Comptes  rend.,  vol.  xliii.  p.  663 :  1856.  M'Munn,  Journ.  Physiol., 
vol.  V.  p.  24:  1885.  Krukenberg,  Virchow's  Arch.,  vol.  ci.  p.  542:  1885.  S. 
Fränkel,  Wien.  med.  Blätter,  Nos.  14,  15,  16  :  1896.  Wien.  klin.  Woehenschr., 
p.  212 :  1896.  G.  Caussade,  Comptes  rend.  Soc.  Mol.,  p.  67 :  1896.  O.  v.  Fürth, 
Zeitschr.  f.  physiol.  Chem.,  vol.  xxiv.  p.  1 :  1897. 

•*F.  and  S.  Marino-Zucco,  loc.  cit. 
5  Wm.  Gull,  Trans.  Clin.  Soc,  Lond. :  1874. 

«William  M.  Ord,  "On  Myxedema,"  Medico-chirurg .  Trans.,  2d  ser.,  vol. 
xliii.  p.  57  :  1878. 


THE   DUCTLESS   GLANDS  431 

degrees  physical  and  mental  feebleness  supervenes,  which  in 
many  respects  resembles  cretinism. 

Ord  had  already  observed  a  shrinking  of  the  thyroid  gland 
and  the  destruction  of  its  follicle  through  the  swelling  connective 
tissue/  but  he  looked  upon  it  merely  as  a  consequence  of  the 
general  myxomatous  new-formation  in  the  connective  tissue. 
He  did  not  yet  recognize  that  the  degeneration  of  the  thyroid 
gland  was  the  primary  factor  in  the  disease.  Ord  called 
attention  to  the  analogy  between  myxedema  and  cretinism, 
and  emphasized  the  fact  that  the  latter  condition  is  frequently 
associated  with  the  colloid  degeneration  of  the  thyroid  gland 
known  as  goiter.^  But  he  did  not  regard  the  change  in  the 
gland  as  being  the  cause  of  cretinism.  The  connection  between 
the  degeneration  of  the  thyroid  gland  and  the  symptoms  of 
myxedema  and  cretinism  was  first  recognized  by  the  Swiss 
surgeons  Reverdin  and  Kocher. 

On  13th  September  1882  J.  L.  Reverdin^  described  before 
the  Medical  Society  of  Geneva  the  effects  of  fourteen  complete 
extirpations  of  goiters,  and  in  April  1883  the  two  Genevese 
surgeons  J.  L.  Reverdin  and  A.  Reverdin  published  in  detail  the 
results  of  removing  goiters  in  twenty-two  cases.*  Of  these  four- 
teen were  complete,  i.  e.,  excision  of  the  whole  diseased  and  of  the 
remaining  sound  tissue  of  the  thyroid  gland.  As  a  consequence 
of  complete  removal,  they  observed  symptoms  which  bore  a 
striking  resemblance  to  those  of  myxedema  and  of  cretinism, 
i.  e.,  swelling  of  the  skin  of  the  face  and  extremities,  diminished 
perspiration,  slowness  and  heaviness  in  the  movements  as  well 
as  in  the  psychical  functions,^  besides  anemia,  a  readiness  to 
fatigue,  a  sensation  of  cold,  and  occasionally  tetany. 

The  extirpation  of  the  thyroid  gland  thus  led  to  a  series  of 
symptoms  which  resembled  myxedema,  in  which  disease  the 
thyroid  gland  undergoes  degeneration.^  We  may  therefore 
conclude  that  it  is  the  absence  of  the  function  of  the  thyroid 
gland  which  causes  the  symptoms  in  both  cases,  viz. — the  ex- 
tirpation and  degeneration  of  the  gland. 

At   the   same    time   as    Reverdin,^   Kocher   was    likewise 

1  Ord,  loc.  cit.,  pp.  60,  67,  72,  73.  B.  Hadden,  Brain,  p.  193 :  1883,  and  Hun 
and  Prudden,  The  American  Journ.  of  the  Med.  Sciences,  vol.  xcvi.:  1888. 

^  Ord,  loc.  cit.  p.  73.  He  here  quotes  the  earlier  authors  who  discuss  the 
question  as  to  the  connection  between  cretinism  and  goiter. 

*  J.  L.  Reverdin,  Revue  med.  d.  I.  Suisse  romande,  2  '^"«Ann.,  p.  539^:  1882. 
'^  Revue  med.  d.  I.  Suisse  romande,  3'«™«  Ann.,  pp.  169,  233,  and  309  :  1883. 

*  Reverdin,  loc.  cit.,  pp.  352  and  355. 

*  Idem,  loc.  cit.,  p.  356. 

'  In  his  first  communication  {Revue  med.  d.  I.  Suisse  romande,  p.  540 :  1882) 
Reverdin  mentions  a  previous  communication  of  Kocher's  on  the  consequences 
of  total  excision  of  goiter. 


432  LECTURE   XXIX 

engaged  at  Berne  in  performing  the  same  operation  of 
complete  extirpation;  and  in  April  1883  he  communicated  the 
results  of  his  abundant  experience  at  the  Congress  of  the 
German  Surgical  Society.^  These  symptoms  which  occurred 
after  total  excision  were  in  all  respects  identical  with  those 
described  by  Reverdin.  If  however  a  minute  portion  of  the 
gland  were  left,  so  that  a  small  fresh  growth  of  thyroid  took 
place/  these  symptoms  did  not  occur.  To  the  latter,  Kocher 
gives  the  name  of  cachexia  strumipriva/  and  he  describes  them 
as  follows  * : 

Soon  after  their  dismissal  from  the  hospital,  or  in  a  few 
cases,  not  until  four  or  five  months  afterwards,  the  patients 
begin  to  complain  of  lassitude,  weakness,  and  weight  in  the 
limbs.  This  is  soon  followed  by  a  sensation  of  cold.  In  the 
winter  time  the  hands  and  feet  become  cold,  swollen,  of  a 
purple  color,  and  chilblains  ensue.  The  mental  condition  is  im- 
paired ;  thought  and  speech  become  slower.  All  movements  get 
slower  and  more  languid.  At  the  same  time  swellings  appear 
on  the  face,  hands,  and  feet ;  in  a  few  cases  these  are  at  first 
temporary,  and  subsequently  they  become  permanent.  The 
thickness  of  the  face  and  the  heaviness  of  the  movements  give 
the  appearance  of  idiocy.  The  whole  skin  seems  swollen  and 
can  only  be  raised  from  the  body  in  large  folds.  Its  surface  is 
dry,  with  scurf  on  the  ears  and  cheeks,  and  the  hair  falls  out. 
In  advanced  cases,  anemia  is  present  to  a  marked  degree.  The 
number  of  red  blood-corpuscles  was  usually  under  4  millions  per 
cb.  mm.,  in  four  cases  it  sank  to  lower  than  2.8  millions,  and  in 
one  case  even  to  2.2  millions.  The  white  blood-corpuscles  were 
relatively  somewhat  increased.  The  anemia  developed  gradually, 
and  grew  progressively  worse  as  time  elapsed  after  the  operation. 
If  at  the  time  of  the  operation  the  patients  were  children  who 
were  growing  fast,  the  stature  was  at  once  arrested  in  a  striking 
manner.  In  many  cases  attacks  of  vertigo  were  observed,  but 
convulsions  were  only  noted  in  one  instance,  that  of  a  girl. 
The  excellent  development  of  the  muscles  formed  a  curious 
contrast  to  the  patients'  complaints  of  feebleness  and  lassi- 
tude. 

The  numerous  excisions  of  goiters  which  have  been  carried 
out  in  Billroth's  hospital  practice  in  Vienna  have  led  to 
divergent  results,  in  so  far  as  the  cases  were  much  more 
frequently  complicated  with  tetany  than  they  were  at  Berne. 

1  Kocher,  Arch.  f.  klin.  Chirurgie,  vol.  xxix.  p.  254  :  1883. 

"^  Idem,  loc.  cit.,  p.  278. 

3  Idem,  loc.  cit.,  p.  28.5. 

•*  Idem,  loc.  cit.,  p.  279,  et  seq. 


THE    DUCTLESS    GLAISTDS  433 

A.  V.  Eiselsberg/  who  has  collected  the  statistics  of  fifty-three 
complete  excisions  performed  in  Billroth's  clinique,  states  that 
attacks  of  tetany  occurred  in  twelve  cases,  eight  of  which  died 
in  consequence.  It  is  noteworthy  that  all  the  twelve  patients 
were  females. 

Kocher  considers  that  the  arrest  of  physical  and  mental 
development  in  cretinism  is  also  due  to  disease  of  the  thyroid 
gland. ^  It  is  true  that  all  cretins  do  not  have  goiters  ;  accord- 
ing to  the  statistics  of  a  French  Commission  the  proportion  is 
somewhat  more  than  75  per  cent.  But  it  must  not  be  over- 
looked that  in  most  cases  cretinous  children  are  descended  from 
goitrous  parents,  and  that  cretinism  is  inherited  through  several 
generations.^ 

From  these  pathological  facts,  a  number  of  physiological 
questions  arise.  We  see  that  the  failure  of  the  thyroid  function 
is  the  signal  for  the  onset  of  the  gravest  physical  and  mental 
disturbances.  What  is  the  connection  between  these  functions  ? 
Are  the  substances  which  act  harmfully  upon  the  organism 
altered  and  rendered  innocuous  as  they  pass  through  the  gland  ? 
Or  are  substances  formed  in  this  organ  which  are  essential  to 
the  performance  of  physical  and  mental  functions  ?  Or  may 
both  these  phenomena  occur  ?  The  fact  already  mentioned 
that  a  small  remnant  of  the  thyroid  gland  is  able  to  take  the 
place  of  the  whole  appears  to  show  that  the  active  principle 
of  the  organ  need  only  be  present  in  a  minute  quantity  in  order 
to  affect  the  total  metabolism,  that  in  fact  it  is  a  question  of 
so-called  ferment-action.  Physiological  experiment  on  animals 
seems  to  confirm  this  view. 

In  1884  Schiff*  published  an  account  of  his  experiments 
on  the  extirpation  of  the  thyroid  gland  in  dogs,  adding  that  he 
had  already  written  about  them  in  1859  but  that  no  notice 
had  been  taken  of  them  by  the  surgical  profession.  Schiff 
found  that  after  complete  extirpation  of  the  thyroid  gland  all 
the  animals  died  from  four  to  twenty-seven  days  afterwards. 
These  experiments  have  been  confirmed  by  many  observers. 
The  symptoms  shown  by  the  animals  subsequent  to  the  oper- 
ation were  however    of  very  variable  character,  not  only  in 

■^  A.  von  Eiselsberg,  "  Ueber  Tetanie  im  Anschluss  an  Kropfoperationen," 
Wien,  A.  Holder  :  1890.  This  author  also  gives  a  complete  account  of  the 
literature  on  the  consequences  of  excision  of  goiters. 

2  Kochner,  loc.  cit.,  p.  298  et  seq. 

^  The  copious  literature  on  the  connection  between  goiters  and  cretinism  is 
quoted  by  A.  Hirsch,  "  Handb.  d.  historisch-geographischen  Patholog.,"  2d 
edition,  Part  II.  pp.  137-140  :  1883. 

*M.  Schiff,  Eev.  med.  d.  I.  Suisse  rom.,  Ann.  iv.  p.  65, 15  F6v.  :  1884.  Transl. 
in  Arch.  f.  exper.  Path.  u.  Pharm.,  vol.  xviii.  p,  25  :  1884. 

28 


434  LECTURE    XXIX 

different  species,  but  also  in  different  individuals  of  the  same 
species.  A  few  of  the  animals  succumbed  rapidly  in  a  few 
days,  frequently  with  the  accompaniment  of  tetany ;  others 
lived  for  some  months  or  even  longer,  and  sank  gradually  from 
general  cachexia.  The  causes  of  this  divergent  behavior  have 
not  so  far  been  explained  in  any  way,  and  the  accounts  are 
very  discordant.^ 

Horsley  ^  found  that  older  animals  survived  excision  of  the 
thyroid  for  a  longer  time  than  young  animals,  and  recalls  the 
observation  of  the  anatomist  Huschke  that  this  organ  is  rela- 
tively larger  in  youth,  and  diminishes  with  age.  The  thyroid 
would  thus  appear  to  take  a  prominent  part  in  the  development 
of  the  tissues.  Moussu,^  Hofmeister,''  and  others  obtained  the 
same  results  as  Horsley. 

In  dogs  and  cats  thyroidectomy  is  usually  fatal.  The 
first  symptoms  are  those  of  general  weakness,  twitchings 
of  the  muscles,  and  disturbance  of  the  regulation  of  the 
temperature.  The  muscular  twitchings  first  appear  as  fibrillar, 
and  subsequently  as  clonic  and  tonic  convulsions,  and  in  the 
worst  form  are  of  an  epileptic  character,  followed  by  Cheyne- 
Stokes  respiration  and  deep  coma.  That  this  muscular  excita- 
tion is  of  central  nervous  origin  was  first  shown  by  Schiff,^ 
who  pointed  out  that  the  muscular  tremors  and  the  convulsions 
were  abolished  by  cutting  through  the  peripheral  nerves.  If 
in  dogs  the  spinal  cord  be  divided  at  the  level  of  the  eighth 
dorsal  vertebra,  the  characteristic  convulsions  which  occur  on 
excision  of  the  thyroid  gland  are  confined  to  the  fore  limbs.^ 
In  a  few  cases  feeble  isolated  twitches  were  also  observed  in 
the  hinder  extremities.  The  impulse  for  the  spasmodic  move- 
ments of  the  extremities  evidently  travels  from  the  brain  to 
the  spinal  cord  by  way  of  the  pyramidal  tracts.  That  the 
disturbances  consequent  upon  thyroidectomy  are  mainly  of 
central  origin  agrees  well  with  the  observations  on  man  :  e.  g., 
the  slowness  of  thought  and  speech  ending  ultimately  in  loss 
of  mental  power.     In  the  case  of  dogs,  death  generally  occurs 

1  On  this  question  see  V.  Horsley,  "  Internat.  Beitr.  z.  wissensch.  Med.," 
Festschr.,  R.  Virchow  gewidmet.,  vol.  i.  p.  382  et  seq.:  1891.  Over  200  publi- 
cations are  here  critically  discussed.  See  further  A.  von  Eiselsberg,  "  Ueber 
Tetanie  im  Anscliluss  an  Kropfoperationen,"  Wien,  A.  Holder,  p.  16  :  1890. 

^Victor  Horsley,  Proc.  Roy.  Soc,  vol.  xl.  p.  7  :  1886. 

3  G.  Moussu,  3fem.  Soc.  Biol.,  p.  271 :  1892. 

*  Hofmeister,  Beitr.  z.  klin.  Chirurg.,  vol.  xi.  :  1894. 

^M.  Schiff,  Rev.  med.  d.  I.  Suisse  rom.,  Ann.  iv.  p.  71  :  1884.  Compare  O. 
Lanz,  Mitth.  a.  Kliniken  u.  med.  Instituten  d.  Schweiz.,  vol.  iii.  p.  512:  1895; 
and  P^r.  de  Quervain,  Virchow's  Arch.,  vol.  cxxxiii.  p.  481  :  1893. 

*0.  Lanz,  Mitth.  a.  Kliniken  u.  med,  Instituten  d.  Schweiz.,  vol.  iii.  p.  516  : 
1895. 


THE    DUCTLESS    GLANDS  435 

within  the  first  fortnight  during  an  attack  of  tetany.^  Occa- 
sionally however,  a  dog  will  survive  the  operation.^ 

In  the  case  of  rabbits  the  accounts  are  so  much  at  variance 
that  for  the  present  no  reliable  deductions  can  be  drawn.' 
E.  Gley'*  found  that  excision  of  the  thyroid  in  rabbits  was 
not  followed  by  death  unless  the  small  accessory  thyroids  ^  were 
removed  at  the  same  time,  and  that  in  these  cases  the  animals 
generally  succumbed  with  signs  of  tetany.  F.  Hofmeister  ^ 
found  that  after  the  extirpation  of  the  thyroid  in  young 
rabbits  cachexia  was  the  invariable  result,  tetany  occurring 
if  the  accessory  glands  were  likewise  removed.  Other  eifects 
observed  by  him  were  retardation  of  the  growth  of  bone  and 
the  ossification  of  the  epiphyses.  Blumenreich  and  Jacoby^ 
contest  Gley's  assertion.  They  found  that  it  made  no  differ- 
ence whether  the  accessory  glands  were  removed  with  the 
thyroid  body  or  not.  The  behavior  of  the  rabbits  on  whom 
thyroidectomy  has  been  performed  varied  greatly  in  every 
particular.  Many  became  cachectic,  but  tetany  seldom  occurred. 
Some  died  soon  after  the  operation,  others  did  not  succumb 
until  months  later  of  some  intercurrent  disorder.  In  the 
animals  suffering  from  cachexia,  atrophy  of  the  lymphoid 
tissues,  and  especially  of  the  thymus,  was  observed,  besides 
disturbances  of  the  biliary  secretion  and  marked  distention 
and  enlargement  of  the  gastric  intestinal  canal.  Lanz  ^  states 
that  all  the  rabbits  in  which  he  excised  the  gland  died  either 
of  acute  or  of  chronic  tetany. 

In  the  case  of  sheep,  goats,  and  donkeys,  cachexia  did  not 
supervene  until  long  after  the  operation.^  In  young  goats  and 
lambs  V.  Eiselsberg^"  noticed  that  the  growth  of  the  bone- 
substance  was  arrested  both  in  length  and  breadth,  and  that 

■T.  M.  Autokratow,  Petersburg.  Wochenschr.,  p.  105  :  1888:  G.  Fano  e.  L. 
Janda,  ArcMvio  medico,  vol.  xiii.  p.  365  :  1889  ;  O.  Lanz,  loc.  cit.  p.  512  :  1895. 

2  Ed.  Wormser,  Pfluger's  Arch.,  vol.  Ixvii.  pp.  533-536:  1897.  Compare 
Drobnik,  Arch.  f.  exper.  Path.  ii.  Pharm.,  vol.  xxv.  p.  136  :  1888  ;  and  R. 
Schwarz,  Lo  Sperimentale,   Fasc.  1 :  1892. 

'  Vide  F.  Hertens,  Zur  Kenntniss  d.  Schilddrüse,"  Diss.,  Göttingen  : 
1890  ;  J.  R.  Ewald  u.  John  Rockwell,  Biol.  Centralbl.,  p.  568  :  1890. 

4E.  Gley,  Arch,  de  Physiol.,  Jan.  and  Apr.  1892,  p.  467  :  1893  ;  p.  101  : 
1894  ;  p.  136  :  1897  ;  and  Pfluger's  Arch.,  vol.  Ixvi.  p.  308  :  1897.  The  literature 
of  the  subject  will  be  found  quoted  here. 

^  For  the  construction  of  the  accessory  thyroid  glands  see  H.  Cristiani,  Arch, 
de  Physiol.,  p.  279  :  1893. 

^  F.  Hofmeister,  Beitr.  z.  klin.  Chir.,  vol.  xi.:  1894. 

'  L.  Blumenreich  and  M.  Jacoby,  Berl.  klin.  Wochenschr.,  p.  327 :  1896 ;  and 
Pfluger's  Arch.,  vol.  Ixiv.  p.  1  :  1896. 

8  O.  Lanz,  3Iitth.  a.  Kliniken  d.  Schweiz.,  vol.  iii.  p.  541  :  1895. 

*  V.  Horsley,  Internat.  Beitr.  z.  wissenschaftl.  3Ied.,  vol.  i.  pp.  390  and  391  ; 
1891. 

'**  A.  V.  Eiselsberg,  Langenb.  Arch.f.  klin.  Chir.,  vol.  ilix.  p.  207  :  1895. 


436  LECTURE   XXIX 

development  of  the  horns  and  hair  was  affected ;  these 
symptoms  were  accompanied  by  a  fall  in  temperature  and 
general  apathy,  recalling  cretinism  in  man.  Tetany  however 
did  not  occur  either  in  these  cases  nor  in  the  case  of  the 
herbivora  upon  which  Lanz  ^  had  performed  thyroidectomy. 
Philipeaux  ^  states  that  removal  of  the  thyroid  gland  had 
no  effect  upon  white  rats,  but  it  may  be  doubted  whether 
these  investigations  were  pursued  far  enough.  Cristiani^ 
showed  that  rats,  as  well  as  domestic  and  field  mice,  have 
accessory  thyroids,  excision  of  which,  together  with  the  main 
gland,  produces  death  from  tetany. 

The  consequences  incident  on  the  extirpation  of  the  thyroid 
glands  in  monkeys  are  described  by  Victor  Horsley  as 
follows  * : 

Fibrillar  muscular  twitchings  of  the  extremities  may  result 
immediately ;  but  as  a  rule  the  animal  remains  quite  healthy 
for  the  first  five  days.  These  twitchings  develop  in  twenty- 
four  hours  into  tetanic  attacks,  which  usually  last  for  about 
twenty  days  and  then  gradually  cease.  At  the  same  time  the 
symptoms  of  myxedema  and  cretinism  slowly  develop  ;  the 
animal  becomes  more  and  more  apathetic,  taking  no  notice 
of  anything,  in  marked  contrast  to  its  former  vivacity.  The 
skin  on  the  face  and  abdomen  becomes  swollen.  According 
to  the  analysis  made  by  Halliburton  this  swelling  is  due  to 
infiltration  with  mucin.  The  salivary  glands  are  markedly 
hypertrophied,  and  the  parotid,  which  normally  yields  a  liquid 
secretion,  now  produces  a  thick  saliva  containing  an  abundance 
of  mucin.  The  blood  shows  extensive  changes  ;  the  red  blood- 
corpuscles  diminish,  the  white  ones  are  at  first  increased  and 
subsequently  likewise  diminish ;  the  blood  now  contains  mucin 
and  the  serum  albumin  is  lessened.  The  body-temperature, 
which  had  risen  somewhat  after  the  operation,  becomes  vari- 
able, and  gradually  falls  after  about  twenty-five  days  far  below 
normal.     The  animal  dies  in  a  state  of  coma. 

In  a  second  communication  ^  Horsley  states  that  he  was 
able  considerably  to  prolong  the  life  of  his  monkeys  if  he  obvi- 
ated the  consequences  of  this  fall  in  their  temperature.  He 
kept  the  animals  in  a  place  maintained  at  a  temperature  of 
32°  C,  and  as  soon  as  nervous  symptoms,  trembling  of  the 
muscles,  &.,  supervened,  he  put  them  in    a   hot-air   bath  of 

^  O.  Lanz,  loc.  cit.,  pp.  513  and  543. 

2  Philipeaux,  Compt.  rend.  Soc.  d.  Biol.,  p.  606  :  1884. 

3  H.  Cristiani,  Arch,  de  Physiol.,  p.  39  :  1893. 

4  V.  Horsley,  Proc.  Roy.  Soc.,  vol.  xxxviii.  p.  6  :  1885. 

5  V.  Horsley,  loc.  cit.,  vol.  xl.  pp.  7  and  8  :  1896. 


THE   DUCTLESS   GLANDS  437 

40.5°  C.  Under  these  conditions  all  the  monkeys,  with  the 
exception  of  the  very  young  animals,  lived  four  to  five  times 
longer  than  the  previous  animals  had  done,  that  is  to  say,  their 
duration  of  life,  instead  of  only  four  to  seven  weeks,  was  now 
extended  to  as  many  months.  The  animals  thus  treated  passed 
through  three  stages — a  neurotic,  myxedematous,  and  atrophic. 
The  symptoms  of  the  first  stage  were  artificially  combated  and 
scarcely  showed  themselves.  The  myxedematous  swellings 
were  likewise  diminished,  and  the  parotid  did  not  become  en- 
larged. The  final  stage  was  marked  by  loss  of  flesh,  functional 
paresis  and  paralysis,  mental  dulness,  lowering  of  the  blood- 
pressure  and  of  the  body-temperature,  ending  in  death  from 
coma. 

On  this  subject  we  may  describe  two  further  observations 
made  by  other  investigators,  v.  Eiselsberg  ^  experimented  on 
a  young  monkey  (^Inuus  ecaudatus).  A  week  after  the  extirpa- 
tion an  attack  of  tetany  supervened,  which  recurred  several 
times,  and  ended  in  complete  apathy.  Nine  weeks  after  the 
operation  the  animal  was  found  dead  in  the  cage.  Dissection 
showed  that  "  the  subcutaneous  cellular  tissue  was  remarkably 
pale,  and  in  patches  somewhat  jelly-like." 

Lanz  ^  records  the  case  of  a  monkey  which  after  removal  of 
its  thyroid  went  into  acute  tetany,  ending  quickly  in  death. 

Very  few  experiments  in  this  connection  have  been  made 
on  birds.  Ewald  and  Rockwell  ^  found  that  pigeons  survived 
the  operation  if  it  were  performed  with  proper  precautions. 
After  the  lapse  of  three  months  they  did  not  notice  any  eifects. 
Perhaps  the  effects  were  overlooked,  and  the  birds  may  not 
have  been  sufficiently  long  under  observation.  Or  must  we 
assume  that  the  thyroid  in  pigeons  is  in  a  rudimentary  condi- 
tion, and  that  other  organs  have  taken  over  its  functions  ? 

The  universal  occurrence  of  the  thyroid  gland  among  all 
the  vertebrata  shows  that  it  is  of  vital  importance  to  the 
organism.  It  is  found  in  all  classes  of  fish,  even  in  the  lowest, 
^■he  petromyzon ;  moreover,  in  the  amphioxus  and  in  the  tuni- 
cata  —  the  invertebrata  which  are  most  nearly  allied  to  the 
vertebrata  —  it  occurs  as  an  extension  of  the  front  portion  of 
intestine  in  a  form  analogous  to  its  embryonic  position  in  the 
higher  animals. 

Cristiani  *  cut  out  the  thyroid  gland  in  lizards  and  snakes, 

^  A.  von  Eiselsberg,  Langenb.  Arch.f.  klin.  Chir.,  vol.  xlix.  pp.  223-226: 1895. 

^O.  Lanz,  Mitth.  a.  Klinik,  d.  Schweiz.,  vol.  iii.  p.  513  :  1895. 

*  J.  R.  Ewald  and  J.  Rockwell,  Arch.  f.  d.  ges.  Physiol.,  vol.  xlvii.  p.  160  : 
1890.     Compare  O.  Lanz,  infra,  p.  486. 

^  Cristiani,  Arch,  de  Physiol.,  vol.  vii.  p.  356 :  1895 ;  and  Pev.  med.  de  la 
Suisse  rom..  p.  37  :  1895. 


438  LECTURE    XXIX 

which  invariably  died  after  a  longer  or  shorter  time.  Lanz^ 
performed  the  same  operation  on  skate  at  the  experimental 
station  at  Naples.  Although  he  could  detect  no  characteristic 
symptoms  of  ill-health,  yet  they  did  not  live  so  long  as  the 
normal  Selachians,  which  were  kept  in  the  aquarium  under  the 
same  conditions. 

The  observation  that  thyroidectomy  is  usually  attended  with 
less  ill-eifects  in  herbivora  than  in  Carnivora  ^  led  to  the  assump- 
tion that  a  meat  diet  was  especially  bad  for  animals  which  had 
been  deprived  of  these  glands.  It  was  thought  that  dogs  and 
cats  bore  the  loss  better  on  a  milk  diet.  ^  On  this  account  a 
chiefly  vegetable  diet  has  been  recommended  for  persons  suffer- 
ing from  cachexia  strumipriva.  Ughetti*  could  not  however 
confirm  the  statements  as  to  the  favorable  influence  of  milk 
and  vegetables  on  the  symptoms  resulting  from  removal  of  the 
thyroid. 

All  observers  are  unanimous  on  one  point,  viz.,  that  the 
untoward  results,  including  death,  of  extirpation  of  the  thyroid, 
are  absent  if  even  a  small  portion  of  the  gland  be  left  behind 
in  its  normal  position.  It  can  be  proved  also  that  removal  of 
the  thyroid  is  without  effect  if  a  little  bit  of  the  gland  be 
transplanted  to  some  other  part  of  the  body.  Experiments 
of  this  nature  had  already  been  carried  out  by  M.  Schiff,  ^  who 
transplanted  the  thyroid  of  one  dog  into  the  abdominal  cavity 
of  another,  and,  after  two  or  three  weeks  extirpated  the  thyroid 
gland  of  the  second  dog.  The  operation  was  successful  in  two 
cases,  in  both  of  which  the  animals  remained  alive  and  well. 
Schiff's  transplantation  experiment  has  been  frequently  con- 
firmed, especially  by  A.  von  Eiselsberg.  ^  This  observer  extir- 
pated the  thyroid  in  fifty  cats,  and  found  that  in  every  case 
the  operation  was  followed  by  tetany  and  death.  In  another 
cat  he  now  excised  only  half  the  gland,  which  he  transplanted 
into  the  abdominal  wall  between  the  peritoneum  and  the  fascia. 
A  month  later  he  removed  the  other  half  of  the  gland.  The 
animal  lived  for  another  two  months,  and  appeared  normal  in 
every  respect.  At  the  end  of  this  time,  i.  e.,  three  months  after 
the  transplantation,  Eiselsberg  cut  out  the  transplanted  bit  of 

^O.  Lanz,  Mitth.  a.  Kliniken  u.  med.  Instituten  d.  Schweiz.,  vol.  iii.  p.  486 : 
1895. 

^G.  Moussu,  Mem.  de  la  Soc.  de  Biol.,  p.  271 :  1892;  0.  Lanz,  loc.  cit.,  p. 
513 :  1895. 

3  Leo  Breisaeher,  Du  JBois'  Arch.,  p.  509 :  1890.  Of.  Moussu,  I.  c;  Fr,  de 
Quervain,  Virchow's  Arch.,  vol.  cxxxiii.  p.  504:  1893;  and  O.  Lanz,  I.  c,  p. 
530. 

*  Ughetti,  Riforma  medica,  December  1892. 

*  M.  Schiff,  Hev.  med.  de  la  Suisse  rom.,  Ann,  4,  p.  425 :  1884. 

*  A.  Freiherr  v.  Eiselsberg,  Wien.  Min.  Wochenschr.,  Jahrg.  v.  p.  81 :  1892. 


THE    DUCTLESS    GLANDS  43^ 

gland,  which  he  found  well  supplied  with  blood  by  two  fairly 
large  vessels,  and  under  the  microscope  presented  a  normal 
appearance.  The  abdominal  wound  was  carefully  closed,  but 
on  the  evening  of  the  next  day  typical  tetany  developed,  and 
the  animal  died  on  the  third  day  after  the  operation.  Eisels- 
berg  carried  out  this  experiment  four  times  with  success. 

These  experiments  are  in  so  far  instructive  as  they  show 
that  the  fatal  results  of  removal  of  the  thyroid  are  not 
dependent  on  interference  with  nerves  or  the  general  circula- 
tion, as  was  formerly  maintained.^  Moreover  the  fatal  results 
could  be  prevented  or  at  any  rate  postponed  by  giving  the 
operated  animals  thyroid  glands  of  the  same  or  other  species 
to  eat,  although  a  continuance  of  this  treatment  was  not 
without  ill-effects  on  the  general  metabolism.  These  were 
especially  marked  by  an  increase  in  the  nitrogenous  excretion 
—  an  increase  which  is  also  observed  even  in  normal  animals.^ 
A  series  of  careful  experiments  by  Fr.  Voit^  on  the  normal 
dog  showed  that  thyroid  administration  caused  not  only  in- 
creased proteid  destruction  but  also  increased  excretion  of  car- 
bon dioxid,  so  that  the  body- weight  may  fall  to  half  its  previous 
amount.^ 

It  is  worth  noting  that,  according  to  Lanz,^  the  subcutane- 
ous injection  of  the  juice  of  the  thyroid  gland  in  normal  animals 
brings  about  atrophy  of  the  thyroid. 

All  attempts  to  isolate  the  active  principle  of  the  thyroid 
gland  have  so  far  led  to  no  satisfactory  result.  Great  interest 
was  excited  by  Baumann's  discovery  of  iodin  ^  in  the  thyroid 
and  by  his  suggestion  that  the  active  principle  of  the  gland 
was  an  iodin  compound.  Previous  observations  had  already 
suggested  the  investigation  of  the  thyroid  for  iodin.  Kocher^ 
who  had  been  treating  goiter  by  means  of  thyroid  extract, 
had  been  struck  with   the  resemblance  of  its  effects  to  those 


^  A  full  and  critical  account  of  the  literature  on  this  subject  is  given  by  V. 
Horsley,  in  the  "  Internat.  Beiträgen  z.  wissensehaftl.  Med.,  Festschr.  E.  Vir- 
chow  gewidmit,"  vol.  i.  p.  372  et  seq.:  1891. 

2  E.  Roos,  Zeitschr.  /.  physiol.  Chem.,  vol.  xxi.  p.  19  :  1895.  B.  SchöndorflF, 
Pflüger's  Arch.,  vol.  Ixiii.  p.  423,  and  vol.  Ixvii.  p.  395 :  1897.  Here  the  com- 
prehensive literature  on  the  influence  of  the  thyroid  gland  on  metabolism  will  be 
found. 

3  Fr.  Voit,  Zeitschr.  f.  Biol.,  vol.  xxxv.  p.  116 :  1897.  Here  a  critical 
account  of  the  earlier  literature  is  given. 

■*  K.  Georgiewsky,  Central b I.  f.  d.  med.  Wissensch.,  No.  27:  1895. 

^  O.  Lanz,  Correspondenzbl.  f.  scMueizer  Aerzte,  Jahrg.  xxv.  p.  293  :  1895. 

^E.  Baumann,  Zeitschr.  f.  physiol-  Chem.,  vol.  xxi.  p.  319 :  1895 ;  vol.  xxii. 
p.  1 :  1887.  3Iünchen.  med.  Wochenschr.,  No.  14  and  20 :  1896.  Baumann  and 
E.  Roos,  Zeitschr.  f.  physiol.  Chem.,  vol.  xxi.  p.  481 :  1896.  E.  Roos,  ibid.,  vol. 
xxii.  p.  16 :  1897  ;  and  "  Ueb.  Schilddrüsentherapie  u.  Jodothyrin,"  Freiburg  and. 
Leipzig,  Mohr :  1897. 


440  LECTUEE   XXIX 

observed  iu  the  ordinary  treatment  with  iodin.  Moreover  it 
had  been  suggested  that  the  occurrence  of  goiter  in  certain 
mountain  valleys  might  be  ascribed  to  the  absence  of  iodin  in 
these  places,  though  subsequent  more  exact  experiments  had 
shown  this  idea  to  be  devoid  of  foundation,  iodin  being  con- 
tained in  the  drinking-water  as  well  as  in  the  plants  of  certain 
valleys  where  goiter  was  endemic/ 

From  the  thyroid  gland  Baumann  extracted  a  substance 
containing  iodin  in  organic  combination.  This  he  regarded 
as  the  active  principle  and  called  iodothyrin.  This  view  is 
open  to  many  objections.  Iodin  is  not  found  in  the  thyroid 
gland  of  all  animals.  Thus  the  gland  of  a  dog  fed  on  meat 
contains  either  no  iodin  or  only  traces,^  and  in  pigs,  oxen,  and 
horses,  iodin  is  found  very  seldom,  and  then  only  in  minute 
quantities.^  Finally  Baumann  himself  states  that  iodin  is  not 
a  constant  constituent  of  the  thyroid  gland  in  man.*  We  cannot 
therefore  regard  the  minute  amount  or  the  entire  absence  of 
iodin  in  goiters  as  the  cause  of  this  disease.^  It  is  possible 
that  the  iodin,  which  exists  in  small  quantities  in  almost 
all  vegetable  food,  is  withdrawn  from  the  circulation  and 
retained  as  a  harmful  substance.  In  man  the  administration 
of  iodin  or  the  treatment  of  wounds  with  iodoform  leads 
to  an  increased  amount  of  iodin  in  the  thyroid.  Baumann 
founds  his  identification  of  iodothyrin  with  the  active  principle 
on  the  fact  that  administration  of  iodothyrin  in  goiter  causes 
disappearance  of  the  tumor.  But,  as  Coindet  ^  pointed  out 
as  early  as  1820,  this  condition  has  also  been  successfully 
treated  with  inorganic  preparations  of  iodin.  In  this  case 
however  much  larger  doses  are  necessary.  But  it  is  possible 
that  the  organic  form  may  be  more  readily  absorbed  and  reach 
the  part  where  its  influence  is  effective.  In  fact  Kocher  suc- 
ceeded in  reducing  goiters  by  the  administration  of  an  artifi- 
cially prepared  iodin  compound  of  casein.'^  Even  before 
Baumann's  discovery,  it  was  known  that  another  artificial  com- 
pound of  iodine  —  tetraiodopyrrol,  had  some  effect  on  goiters.  ^ 

^  An  account  of  the  comprehensive  literature  on  this  subject  is  given  by  A. 
Hirsch,  "  Handb.  d.  historisch-geographischen  Pathologie,"  Stuttgart,  Enke, 
Abth.  ii.  pp.  135  and  136 :  1883. 

2  Baumann,  Zeitsehr.f.  physiol.  Chem.,  vol.  xxii.  p.  14:  1896. 

ä  Töpfer,  Wien.  klin.  Wochenschr.,  p.  141 :  1896. 

*  Baumann,  loc.  dt.,  pp.  3-12. 

^  Baumann,  München  med.  Wochenschr.,  No.  14  :  1896. 
^  J.   Fr.    Coindet,  Bibliotkhque  universelle  de   Genhve,  vol.  xiv.  p.   190 : 
1820. 

■^  Ed.  Wormser,  Pflüger's  Arch.,  vol.  Ixvii.  p.  529  :  1897. 

*  O.  Schorndorff,  "  Beitr.  z.  therapeutischen  Verwerthbarkeit  des  Jodes," 
Diss.,  Würzburg:  1889. 


THE   DUCTLESS    GLANDS  441 

It  is  also  claimed  that  good  results  have  been  obtained  with 
injections  of  iodoform.^  Certain  sea  animals  and  plants  which 
contain  iodin  have  been  used  as  medicaments,  and  especially 
in  cases  of  goiter,  for  hundreds  of  years  before  the  discovery 
of  iodin.  Harnack  ^  has  recently  given  an  interesting  account 
of  these  iodin  drugs.  As  I  have  already  mentioned,  Kocher  ^ 
observed  even  in  the  earliest  attempts  to  relieve  the  struma  with 
thyroid  preparations,  how  much  the  mode  of  action  resembled 
that  of  the  long-used  iodin.  As  a  final  proof  that  iodothyrin 
was  the  active  principle  of  the  thyroid.  Baumann  stated  that 
the  tetanic  convulsions  occurring  in  dogs  as  a  consequence  of 
thyroidectomy  were  prevented  by  the  administration  of  iodo- 
thyrin (2-3  grs.  per  diem).*  This  statement  could  not  how- 
ever be  confirmed  by  Gottlieb  and  Wörmser.  Gottlieb  ^ 
showed  in  three  experiments  that  the  tetany  and  death  resulting 
from  the  extirpation  of  the  thyroid  could  not  be  prevented  by 
the  administration  of  iodothyrin.  Kocher's  pupil,  E.  Wörmser,^ 
comes  to  a  similar  conclusion.  He  finds  that  iodothyrin  was 
ineffective  either  in  preventing  an  attack  or  in  stopping  an 
attack  which  had  already  begun  ;  whereas  all  attacks  of  tetany 
can  be  kept  off  and  the  life  of  the  animal  preserved  for  a  long 
time  by  administration  of  the  whole  thyroid  gland. 

All  other  efforts  to  isolate  the  effective  principle  of  the 
thyroid  gland  have  been  equally  unsuccessful.'^  None  of  the 
substances  which  have  been  isolated  from  the  gland  have  been 
of  any  use  for  counteracting  the  effects  of  thyroidectomy.  The 
only  preparations  which  were  of  any  value  were  those  which 
contained  the  proteids  of  the  gland,  though  these  were  less 
effectual  than  the  whole  gland,  dried  at  65°  C,  which  in  its 
turn  was  inferior  to  the  fresh  raw  gland. 

At  present  there  is  no  evidence  against  the  view  that  the 
active  principle  of  the  gland  belongs  to  the  class  of  labile  proteids, 
a  class  including  all   those  substances  which  have  the  most 

^  R.  V.  Mosetig-Moorhof,  Wien.  Press.,  No.  1  :  1890. 

2E.  Harnack,  München,  med.  Wochenschr.,  No.  9  :  1896. 

ä  Kocher,  Correspondenzbl.  f.  schweizer  Äerzte,  vol.  iiv.  p.  6  :  1895. 

*  Baumann  and  E.  Goldmann,  München,  med.  Wochenschr.,  No.  47  :'  1896. 
F.  Hofmeister,  Deutsch,  med.  Wochenschr.,  p.  354  :  1896.  H.  Hildebrandt,  Berl. 
klin.  Wochenschr.,  p.  826  :  1896.  A.  Irsai,  3fünchen.  med.  Wochenschr.,  p.  1249  : 
1896. 

^  Gottlieb,  Deutsch,  med.  Wochenschr.,  -p.  235:  1896.  Compare  A.  Notkin, 
Wien.  klin.  Wochenschr.,  No.  43  :  1896. 

^Edm.  Wörmser,  Pflüger' t  Arch.,  vol.  Ixvii.  p.  505  :  1897. 

'  In  this  connection  read  :  Drechsel,  Physiol.  Centralhl.,  vol.  ix.  p.  705  :  1895  ; 
S.  Fränkel,  Wien.  med.  Blätter,  No.  48 :  1895 ;  Nos.  13-15  :  1896 ;  J.  Notkin, 
Wien.  med.  Wochenschr., 'So.  45,  p.  824:  1895;  Virchoiv's  Arch.,  vol.  ciliv.; 
Suppl.,  p.  224:  1896;  ß.  Hutchinson,  Centralbl.  f.  d.  med.  Wi^sensch., -p.  209 : 
1896. 


442  •  LECTURE    XXIX 

potent  influence  on  the  body  functions,  viz.,  the  most  useful 
ferments  and  the  most  virulent  poisons.  (Compare  Lectures 
XI.  and  XXVII.) 

We  may  conclude  that  the  assumption  that  poisonous 
products  of  metabolism  are  destroyed  in  the  thyroid  gland 
must  be  discarded  as  extremely  improbable.  We  could  not, 
on  such  an  hypothesis,  explain  the  fact  that  a  very  minute 
fragment  of  the  gland  left  behind  at  the  operation  or  trans- 
planted to  some  other  part  of  the  body,  is  sufficient  to  prevent 
all  the  usual  effects  of  thyroidectomy.  Nor  does  it  seem 
probable  that  the  blood  flow  through  the  small  vessels  of  the 
gland  can  be  sufficiently  abundant  for  such  a  process  of  puri- 
fication to  take  place  to  any  considerable  extent.  It  is  much 
more  probable  that  the  gland  is  continually  giving  off  to  the 
blood  minute  quantities  of  a  ferment-like  substance,  which 
influences  the  metabolism  in  other  organs  of  the  body.  We 
thus  come  to  the  same  conclusion  as  we  arrived  at  in  dealing 
with  the  internal  secretion  of  the  pancreas.     (Compare  p.  398.) 

Attempts  have  naturally  been  made  to  utilize  in  therapeutics 
the  various  results  of  chemical  and  vivisectional  experiments 
described  above.  The  first  object  of  these  attempts  was  to 
counteract  the  cachexia  strumipriva  which  supervenes  as  the 
result  of  total  extirpation  of  the  gland  for  goiter.  But  they 
were  naturally  extended  to  the  treatment  of  myxedema  and 
cretinism.  The  method  first  used  was  that  of  transplantation 
of  the  gland,  but  it  was  found  that  the  transplanted  gland 
underwent  absorption  after  a  short  time,  so  that  only  transient 
improvement  was  effected.^  The  result  was  equally  unsatis- 
factory in  a  case  where  the  human  gland  itself  was  used.  A 
female  cretin,  thirty-three  years  of  age,  developed  severe  myx- 
edema with  epileptic  attacks  and  apathy,  as  the  result  of 
total  extirpation  of  the  thyroid  for  goiter.  Bircher  ^  therefore 
transplanted  into  the  abdomen  of  this  patient  a  bit  of  the 
thyroid  gland,  which  he  had  just  removed  from  another  patient 
in  an  operation  for  goiter.  Within  a  few  days  the  patient  was 
markedly  better,  and  at  the  end  of  four  weeks  her  former 
intellectual  activity  and  power  of  work  were  fully  restored. 
After  this  came  a  relapse,  and  the  condition  grew  steadily 
worse  for  four  weeks.  A  second  transplantation  was  therefore 
carried  out  in  similar  manner  to  the  first.  Three  months 
after  the  second  transplantation  the  woman  was  perfectly  well 

^  Lannelongue,  Wien.  med.  Blätter,  No.  13  :  1890 ;  P.  Merklen  and  Ch. 
Walther,  Mercredi  mtd..  No.  46  :  1890. 

H.  Bircher,  "Das  Myxödem  u.  d.  cretinische  Degeneration";  Volkmann's 
"  Sammlung  klinischer  Vorträge,"  No.  357,  pp.  12-16 ;  and  Nachtrag,  p.  32  :  1890. 


THE    DUCTLESS    GLANDS  443 

and  worked  the  whole  day ;  but  six  months  later  the  epileptic 
attacks  recurred.  In  the  same  way  Kocher  ^  succeeded  in  pro- 
ducing only  a  temporary  improvement  in  his  attempts  to  treat 
cachexia  strumipriva  by  transplantation  of  the  gland  of  men  or 
animals. 

It  seems  therefore  that  transplantation  succeeds  only  when 
the  transplanted  piece  of  gland  becomes  vascularized — a  proc- 
ess which  so  far  has  occurred  only  in  the  transplantation  in 
healthy  animals  when  their  own  gland  has  been  used. 

This  method  had  therefore  to  be  given  up  and  trial  was 
made  of  the  introduction  of  the  active  principle  of  the  gland 
by  subcutaneous  injection  or  administration  by  the  mouth. 
The  latter  mode  has  proved  to  be  the  simpler  and  more  effective. 
The  results  have  been  wonderfully  good.  The  myxedematous 
swelling  diminishes  and  the  general  bodily  and  mental  condi- 
tion improves  in  a  marked  manner.^  Relapse  however  occurs 
at  once  if  the  treatment  be  discontinued.  Renewed  administra- 
tion of  thyroid  counteracts  these  effects  for  a  time,  but  appar- 
ently not  permanently,  since,  as  we  have  already  seen  in  experi- 
ments on  animals,  disturbances  of  metabolism  occur,  such  as 
increased  output  of  nitrogen,  showing  a  correspondingly  in- 
creased proteid  disintegration  in  the  tissues.^  The  same  result, 
but  to  a  less  extent,  follows  the  administration  of  thyroid  in 
healthy  men,*  and  leads  in  time  to  diminished  body-weight,^ 
and  finally  to  glycosuria*'  and  albuminuria.^ 

These  experiences  have  impressed  on  surgeons  the  necessity 
of  avoiding  where  possible  complete  extirpation  of  a  goitrous 
thyroid,  and  the  operation  is  now  only  performed  in  certain 
cases  of  malignant  tumors,  such  as  cancer  or  sarcoma.  Thus 
the  clinical  records  gleaned  by  Kocher,  Reverdin,  and 
Billroth  from  cases  in  which  total  extirpation  of  the  thyroid  in 

■•Kocher,  Correspoiulenzbl.  f.  schweizer  Äerzte,  Jahrg.  23,  p.  529:  1893;  and 
Jahrg.  25,  p.  9  :  1895. 

2  Mackenzie,  Brü.  Med.  Journ.,  Oct.  29  :  1892.  Vermehren,  Deutsch,  med. 
Wochenschr. ,  March  16,  1893.  Yassale,  Eiv.  sperimentale,  yol.  xix.  Fase.  IL, 
III.  :  1893.  Leichenstein,  Deutsch,  med.  Wochenschr.,  Nos.  49-51 :  1893. 
Costanzo,  Rivista  Veneta  di  scienze  mediche,  vol.  xx.  Fase.  IL :  1894.  Palleske, 
Deutsch,  med.  Wochenschr.,  No.  7  :  1895.  O.  Lanz,  Correspondenzbl.  d.  schweizer 
Aerzte,  Jahrg.  25,  p.  296 :  1895. 

^Mendel,  Deutsch,  med.  Wochenschr., 'No.  2:  1893.  Napier,  Lancet,  Sept. 
30,  1893.  Vermehren,  Deutsch,  med.  Wochenschr.,  No.  43:  1893.  Ord,  Brit. 
Med.  Journ.,  vol.  ii.  p.  212  :  1893. 

*  Vermehren,  loc.  cit.,  A.  Dennig,  München,  med.  Wochenschr.,  Nos.  17  and 
20.     Bleibtreu  and  Wendelstadt,  Deutsch,  med.  Wochenschr.,  No.  22  :  1895. 

5  Reinhold,  Münch.  med.  Wochenschr.,  July  31,  1894.  Bruns,  Deutsch,  med. 
Wochenschr.,  Oct.  11,  1894. 

ß  C.  A.  Ewald,  Berl,  Hin.  Wochenschr.,  Nos.  2  and  3 :  1895.  A.  Dennig, 
loc.  cit.     Bleibtreu  and  Wendelstadt,  loc.  cit. 

'  A.  Dennig,  loc.  cit. 


444  LECTURE   XXIX 

man  for  goiter  has  been  performed,  will  be  of  inestimable  value 
for  future  physiological  research,  since  they  can  never  be 
repeated. 

As  already  mentioned  (p.  441)  attempts  have  been  made  to 
treat  goiter  itself  by  administration  of  thyroid  gland.  Rein- 
hold^  obtained  an  almost  complete  disappearance  of  the  tumor 
in  five  cases  out  of  six  that  he  treated  in  this  manner,  and 
Bruns^  had  equal  success  in  nine  out  of  twelve  cases.  Myxe- 
dema and  cretinism  have  also  been  successfully  treated  by  the 
administration  of  thyroid  gland,^  as  also  by  transplantation, 
though  in  the  latter  case  the  good  effects  have  been  only 
temporary.* 

The  cachexia  and  bodily  and  mental  weakness,  which 
sometimes  supervene  after  partial  thyroidectomy,  have  also 
been  treated  with  great  success  by  the  administration  of  raw 
thyroids.^ 

Finally  a  large  number  of  the  most  diverse  disorders  have 
been  subjected  to  treatment  with  thyroid.  Among  these  we 
may  mention  obesity,  psoriasis,  eczema,  lupus,  syphilis,  leprosy, 
exophthalmic  goiter,  acromegaly,  mental  diseases,  diabetes, 
tuberculosis,  uric  acid  diathesis,  rickets,  &c.,  &c.  It  is 
however  impossible  at  present  to  say  how  far  this  mode  of 
treatment  has  been  of  good  or  of  harm  in  these  various 
maladies.^ 

Before  leaving  the  subject  of  the  thyroid  gland,  I  may 
mention  the  observations  which  point  to  some  connection 
between  the  activity  of  this  organ  and  the  sexual  functions. 
Impaired  development  and  retarded  descent  of  the  testes  has 
been  observed  after  excision  of  the  thyroid  in  young  animals. '^ 

1  Reinhold,  loc.  cit. 

^  P.  Bruns,  JBeitr.  z.  klin.  Chirurgie,  12, 1894.  Compare  also  Kocher,  Corre- 
gpondenzbl.  f.  schweizer  Aerzte,  vol.  xxv.  p.  3  :  1895.  O.  Lanz,  idem,  Nos.  2  and 
10 :  1895.  A.  Irsai,  B.  Vas,  and  Gesa  Gara,  Beut.  med.  Woch.,  No.  28 :  1896. 
G.  R.einbach,  Mitt.  a.  d.  Grenzgeb.  d.  Med.  u.  Chir.,  vol.  i.:  1896.  H.  Stabel, 
Berl.  klin.  Woch.,  No.  5  :  1896.  O.  Angerer,  Munch,  med.  Wochenschr.,  No.  4  : 
1896.     P.  Bruns,  Bruns'  Beiträge,  vol.  ivi. :  1896. 

^  Beadle,  Lancet,  Feb.  17,  1894.  E.  Mendel,  Deut.  med.  Woch.,  No.  7  :  1895. 
C.  A.  Ewald,  Berl.  klin.  Woch.,  Nos.  2,  3,  and  30 :  1895.  O.  Lanz,  Correspond- 
enzbl.  f.  schweizer  Aerzte,  Nos.  2  and  10 :  1895.  R.  Abrahams,  Med.  Record, 
April,  1895.  Vermehren,  "Studien  üb.  Myxödem,"  Diss.  Copenhagen:  1895. 
Middleton,  Glasgow  Journ.,  Feb.  1896.  W.  H.  George,  Brit.  Med.  Journ.,  Sept. 
12,  1896.  Rushton  Parker,  ibid.,  June  27,  1896.  H.  H.  Vinke,  Med.  News,  No. 
12  :  1896. 

*  v.  Gernet,  Zeitschr.  f.  Chirurgie,  vol.  xxxix. :  1894. 

5  Angerer,  München,  med.  Wochenschr.,  No.  28:  1894.  Sonnenburg,  Lan- 
genb.  Arch.,  vol.  xlviii.:  1894. 

^  The  literature  on  this  subject  will  be  found  in  a  paper  by  E.  Roos,  "  Ueb. 
Schilddriisentherapie  u.  Jodothyrin,"  Freiburg  and  Leipzig,  Mohr  :  1897. 

">  A.  V.  Eiselsberg,  Arch.  f.  klin.  Chir.,  vol.  xlix.  pp.  216  and  225  :  1895. 


THE    DUCTLESS    GLANDS  445 

Langhans  found  the  testes  atrophied  in  cretins.'  A  connection 
of  the  thyroid  gland  with  the  sexual  functions  has  been  known 
of  for  a  long  time.^  Swelling  of  the  gland  is  often  observed  at 
the  menstrual  period  as  well  as  during  pregnancy,  parturition, 
and  lactation,  though  this  does  not  occur  in  the  majority  of 
cases.  Thus  J.  Fischer^  could  only  detect  swelling  of  the 
thyroid  gland  in  two  cases  out  of  fifty  during  menstruation, 
and  in  only  one-third  of  the  cases  in  pregnancy.  The  more 
frequent  occurrence  of  myxedema  in  women  is  worthy  of 
note.  According  to  the  results  collected  by  a  committee  of  the 
Chemical  Society,^  out  of  every  hundred  cases  of  myxedema, 
eighty-six  are  women  and  only  fourteen  men.  In  the  ovaries 
of  cretins,  Langhaus'  found  the  follicles  but  slightly  devel- 
oped ;  only  a  few  follicles  were  in  a  process  of  growth,  while 
the  majority  remained  in  their  primitive  condition.  In  the 
transplantation  experiment  of  Bircher^s,^  which  I  mentioned 
above,  the  awakening  of  the  psychical  functions  was  attended 
with  a  restoration  of  the  sexual  functions.  Menstruation  which 
had  ceased  for  a  year,  occurred  again  regularly  after  the  trans- 
plantation. 

A  connection  of  the  gland  with  sexual  life  seems  to  be  in- 
dicated by  the  fact  to  which  Schölein^  draws  attention,  viz., 
that  the  frequency  of  goiter  shows  two  maxima,  one  at  the  time 
of  puberty  and  the  other  during  senile  involution. 

An  interesting  observation  has  been  made  on  birds  by 
Lanz,*  who  took  two  young  hens  of  the  same  brood  and  in  one 
of  them  excised  the  thyroid  gland.  The  operated  animal 
developed  more  slowly  and  was  smaller  than  the  other.  Its 
comb  was  also  ill-formed.  There  was  also  a  great  difference 
in  the  laying  powers  of  the  two  hens ;  the  one  which  had  lost 
its  thyroid  laid  only  one  egg  four  months  after  the  extirpation. 
This  had  a  shell  as  thin  as  paper  and  weighed  only  5  grms., 
whereas  an  ordinary  hen's  egg  weighs  50  to  60  grms.  In 
another  experiment  Lanz  took  nine  hens,  all  eighteen  months 
old,  and  to  one  of  them  gave  10  to  30  grms.  of  thyroid  gland 
every  day  to  eat.     While  the  other  eight  hens  laid  altogether 

^  Th.  Langhans,  V-irchow's  Arch.,  vol.  cxlix.  p.  155:  1897.  The  views  of 
earlier  authors  on  the  subject  of  the  sexual  organs  in  cretins  are  quoted  here. 

An  account  of  our  knowledge  on  this  noatter  is  given  by  H.  W.  Freund, 
Deut.  Zeitschr.  f.  Chir.,  vol.  xviii.  p.  213 :  1883. 

3  J.  Fischer,  Wien.  med.  Woch.,  Nos.  6,  7,  8  and  9 :  1896. 

*  Clin.  Soc.  Trans.,  supplement  to  vol.  xxi.    London :  1888. 

5  Langhans,  loc.  cit. 

6  Bircher,  loc.  cit.,  p.  3407. 

'J.  L.  Schönlein,  "Pathologie  u.  Therapie,"  part  i.  p.  81,  St.  Gallen: 
1846. 

*  O.  Lanz,  Mitth.  a.  d.  Kliniken  d.  Schweiz,  iii.  p.  540:  1895. 


446  LECTURE   XXIX 

forty-two  eggs  in  twenty-three  days,  the  ninth  that  was  fed 
with  thyroid  laid  in  the  same  time  sixteen  eggs,  i.  e.,  three 
times  as  many  as  the  others.  The  weight  of  these  eggs  gradu- 
ally increased  ;  the  last  egg  laid  before  the  thyroid  feeding  was 
begun  weighed  50  grms.,  while  afterwards  the  weight  gradually 
rose  to  60  grms. 

I  may  now  say  a  few  words  about  the  anterior  glandular 
portion  of  the  pituitary  body.  The  position  of  this  gland 
renders  it  extremely  inaccessible  to  operative  interference,  so 
that  attempts  at  its  removal  are  usually  attended  with  fatal 
results  from  the  operation  itself  and  teach  us  nothing  con- 
cerning the  significance  of  the  organ.  The  pituitary  body  has 
sometimes  been  found  hypertrophied  in  dogs  and  rabbits  after 
extirpation  of  the  thyroid,^  and  hypertrophy  has  also  been 
found  in  man  in  sporadic  cretinism,  accompanying  atrophy  of 
the  thyroid,^  as  well  as  in  one  case  of  goiter.^  These  facts,  as 
well  as  the  occurrence  of  iodin  in  the  human  pituitary  body,* 
have  led  to  the  assumption  of  some  analogy  between  the  fiinc- 
tions  of  this  body  and  those  of  the  thyroid. 

Rogo witsch  regards  the  pituitary  body  as  equivalent  to  the 
thyroid,  and  emphasizes  the  fact  that  rabbits,  which  withstand 
the  effects  of  thyroidectomy  longer  than  do  dogs  or  cats,  pos- 
sess also  relatively  larger  pituitary  bodies.  In  the  rabbit  the 
thyroid  is  only  three  times  as  heavy  as  the  pituitary,  whereas 
in  dogs  and  cats  it  is  fifteen  to  twenty  times  as  heavy .^ 

Finally  the  view  has  been  put  forward  that  disease  of  the 
pituitary  leads  to  disorders  of  nutrition  as  extensive  as  those 
following  diseases  of  the  thyroid.  Just  as  the  latter  leads  to 
myxedema  and  cretinism,  so  the  abolition  of  the  functions  of  the 
pituitary  body  is  supposed  to  lead  to  acromegaly,  i.  e.,  a  morbid 
increase  in  the  growth  of  the  bones.  In  fact  in  some  cases  and 
indeed  in  all  since  attention  has  been  directed  to  the  point, 
hypertrophy  or  disease  of  the  pituitary  body  has  been  found 
post  mortem  in  cases  of  acromegaly.^ 

IN.  Rogowitsch,  Arch.  d.  physioL,  4  Ser.,  vol.  ii.  p.  419:  1888;  F.  Hof- 
meister, Beitr.  z.  klin.  Chir.,  vol.  xi.  p.  2:  1894;  L.  Blumreich  and  M.  Jacoby, 
Pflilger's  Arch.,  vol.  Ixiv.  p.  1 :  1896,  could  not  confirm  this  statement  as  regards 
rabbits,  nor  J.  R.  Ewald  and  J.  Rockvirell  as  regards  pigeons,  Pflüger's  Arch., 
vol.  xlvii.  p.  170 :  1890. 

2  Bourneville  and  Bricon,  Arch.  d.  Neurologie,  1886. 

'  K.  Wolf,  Ziegler's  Beitr.,  vol.  xiii. :  1893. 

^Schnitzler  and  Ewald,  Wien.  klin.  >Foc/i.,  No.  29 :  1896. 

^  N.  Rogowitsch,  Beitr.  z.  pathol.  Anat.  u.  allgem.  Pathol,  v.  Ziegler,  vol.  iv.: 
1889.  Compare  H.  Stieda,  "  Ueb.  d.  Verhalten  d.  Hypophysis  des  Kaninchens 
nach  Entfernung  der  Schilddrüse,"  Diss.,  Königsberg,  1889,  and  Ziegler's  Beitr., 
vol.  vii.  p.  537  :  1890. 

*  P.  Marie  and  G.  Marinesco,  Arch,  de  mtd.  experim.,  July  1,  1891.  F.  A. 
Packard,  American  Journ.,  June,  1892;   K.  Wolf,  Ziegler's  Beitr.,  vol.  xiii.: 


THE   DUCTLESS   GLANDS  447 

IJnless  the  methods  of  vivisection  and  asepsis  make  some 
unexpected  advance,  we  must  in  the  near  future  await  an 
increase  of  our  knowledge  on  this  point  rather  from  the  side  of 
pathological  anatomy  and  clinical  observation. 

1893.  E.  Caton  and  F.  T.  Paul,  Brit.  Med.  Journ.,  Dec.  30,  1893.  J.  Arnold, 
Virchow's  Arch.,  vol.  cxxxv.:  1894.  M.  Dallemagne,  Arch,  de  med.  exp., 
vol.  vii.:  1895.  Comini,  Arch,  per  le  scienze  med.,  vol.  xv.  No.  21,  p.  435  :  1896. 
E.  Eoxburgh  and  A.  J.  Collis,  Brit.  Med.  Journ.,  p.  63,  July  11,  1896. 
A.  Tamburini,  Riv.  sperim.  di  Freniatria  e  di  Med.  legale,  vol.  ix.:  1896.  Ad. 
Strümpell,  "Lehrb.  d.  speciellen  Path.  u.  Therapie,"  10th  ed.,  vol.  iii.  p.  165: 
1896. 


INDEX 


Absorption  of  food,  3-4,  187-190,  360- 

363 
Acetic  acid — 

Avidity,  136 

Decomposition,  157 

Heat  equivalent,  62 
Aceto-acetic  acid  in  diabetes,  391 
Aceton,  391 ;  in  diabetic  coma,  403 
Acid — 

Intoxication,  404 

Mineral,  secreted  by  lower  animals, 
133 
Acids — 

After  extirpation  of  liver,  311 

Elfect  of,  on  ammonia  excretion,  292  ; 
on  toxalbumins,  418 

In  stomach,  143 

Of  bile,  177,  182,  185 

Of  intestinal  contents,  174 

Of  urine,  321 

Vegetable,  321 

Weaker  and  stronger,  135-136 
Acromegaly,  446 
Adenin,  77,  314 
Adenoid,    tissue,   action    on    peptones, 

197-198 
Aerotonometer,  262 
Albumin,  43-54 

Alkali-,  45 

Egg-,  45,  52 

Serum-,  45 
Albuminuria  in  fever,  426-427 
Alcohol,  117-119 

Action  of,  in  moderation,  117-121 ;  in 
excess,  121-122 

As  food,  357 

Energy  derived  from  combustion  of, 
117 

Fermentation  product,  143 

Influence  on  fat  formation,  369 

Value  as  a  medicine,  122 
Aleuron-crystals,  46 
Alimentary  canal,  gases  of,  276,  280 
Alkalies — 

Action  on  toxalbumins,  418 

In  diabetes,  406 
Alkaline  phosphates  of  plasma,  264 
Alkaloids — 

Isolation    from    bacterial    products, 
409-411 

Containing  cholin,  76 
Allantoin,  304 
Alloxan,  305 
Alumina — 

Colloidal  form,  44 

In  soil,  25 
Aluminium,  circulation  of,  25 
Amanita  phalloides,  416 
Amido-acetic  acid,  56,  n.  2. 


Amido-acids,  54 

Aromatic,  257 

Constitution,  288 

Formation,  167-168 

Influence  on  urea,  289 
Ammonia — 

After  extirpation  of  liver,  311 

Efiect  of  acids  on  excretion  of,  292 

Elimination  of,  in  fever,  425 

Hydrogen  from,  14 

Nitrogen  from,  17 

Precursor  of  urea,  290 
Ammonia,  nitrite  of,  18 
Ammonium    carbamate,    precursor    of 

urea,  293 
Ammonium  cyanite,  precursor  of  urea, 

292 
Amebse,  3-4 
Anemia,  379 
Animal  heat — 

And  vital  functions,  64 

Source  of,  31-34 
Animal  life  and  vegetable,  interdepen- 
dence, 14,  16 
Animals — 

Containing  chlorophyll,  39 

Contrasts  between  plants  and,  38-40 
Anthrax  bacillus — 

Action  of  gastric  juice  and  HCl  on,  142 

Influence  of  temperature  on  activity, 
421 
Antipyretic  remedies  in  fever,  421,  n.  2 
Appetite,  stimulation  of,  11 
Arcellfe, possible  psychical  processes  in, 7 
Argenin,  289 
Aromatic  hydrocarbons,  258 

Sulphates,  256 ;  in  urine,  324 
Arsenic,  influence  on  nitrogen  excre- 
tion, 121 
Arsenical  poisoning,  426 
Artificial  feeding  of  infants,  108-112 
Ascitic  fluid,  226 
Ash— 

Of  dog's  blood,  83 ;  dog's  blood 
serum,  83 ;  dog's  milk,  S3,  377 ; 
milk  of  ditferent  mammals,  105 ; 
puppy,  377  ;  sucking  animals,  83 

Of  meat  extract,  lime  in,  126 
Aspartic  acid  in  the  body,  289 

T5  A  PTT^'TIT  A 

Action  of  HCl  on,  131-132,  142-143 ; 

heat  on,  161 ;    leucocytes  on,  222- 

223 
Action  on  cellulose,  163;  on  formate 

of  lime,  156-157 
Optimum  temperature,  420-421 
Relation  to  infectious  diseases,  408, 

411-413 


29 


449 


450 


INDEX 


Bacteria — continued 

Eole    of,    in    the     maintenance    of 
organic  life,  17-19 
Bacterial  poisons,  409-415 
Benzoic  acid,  282 
Benzol,  oxidation  of,  256 
Benzolic  acid,  formation  of,  248 
Beta  altissima,  102 
Bile,  176-186 

Acids,  177-178 ;  their  origin,  336 

Action  on  fat,  183-184 

Antiseptic  property,  185-186 

Composition,  180-181 

Constituents,  176-180 

Functions,  182-186 

Pigments,  178-179  ;  their  origin,  336, 
337 
Bilirubin,  178 ;  origin  of,  337 
Biliverdin,  178 
Blood- 
Changes  in,  in  fever,  425-426 

Circulation  of,  5 

Coagulation  of,  200-205 

Corpuscles   (red),   200,   206-215;    de- 
struction of,  340 ;  in  fevers,  425 

Effect  of  extirpation  of  spleen  on, 
230  ;  CO2  on,  265 

Defibrinated,  200,  205,  207-211 

Fat  in,  189-190 

Fibrin,  200,  212-215 

Gases  of,  238 ;  in  diabetic  coma,  404 

Leucocytes,  202,  204,  222,  425 

Peptones  in,  194-195 

Pigment,  fate  of,  337 

Plasma,  205-206,  212-215,  218,  225 

Serum,  200,  206-211,  213-215,  216,  225, 
262 

Sodium  in,  208 

Sugar  in,  188-189,  388 

Tension  of  CO2  in,  262 
Blood-vessels  in  fever,  423 
Bone-substance,  effect  of  extirpation  of 

thyroid  on,  435-436 
Bones,  fluorin  in,  24 
Bouillon,  food  value  of,  124-128 
Brain,  injury  and  temperature,  423 
Bread,  digestion  of,  69,  72-74 
Bromin,  circulation  of,  24 
Brown  bread,  69,  72-73 
Burial  versus  cremation,  18-19 
Burns,  effect  of,  275 
Butyric  fermentation,  142-143,  158- 
159,  251,  277 

Cachexia  strumipriva,  432, 435, 442-443 
Caffein — 

Action,  123-124 

Effects,  319 

Occurrence,  123 
Calcium,  circulation  of,  20 
Cane-sugar,  decomposition,  155-156 
Carbohydrates — 

A  source  of  energy,  349 

Absorption  of,  71 

As  food,  42,  43,  60-74 

Decomposition  of,  255 

Diminished  assimilation  of,  389 

Effect  on  glycogen,  345 

Fat  formation  from,  366 

Pancreatic  digestion  of,  162-163 
Carbon,  circulation  of,  13-14 


Carbonate  of  soda  in 

Intestinal  juice,  174-175 

Pancreatic  juice,  165 
Carbonic  acid — 

Balance  of  oxygen  and,  14-17 

Circulating  medium  of  carbon,  13-14 

Effects  of  its  retention,  268 

Excretion  of,  221,  439 

In  respiration,  261-271 

Intoxication,  404 

Of  muscle,  350 

Output  in  fever,  422 

Production  in  intestines,  278 

SolubUity  of,  261 

Struggle  with  silicic  acid,  15-16 

Tension  in  tissues,  267 
Carbonic  oxide,  effects  of,  242;   hemo- 
globin, 240 
Carmine,  excretion  by  kidneys,  318 
Cartilage,    gelatin  of,   55;    sodium  in, 

102-103 
Caseinogen,  109 
Cell  life,  continuity  of,  64-65 
Cells,  functions  of,  3-6,  137,  147 
CeUulose,  digestion  of,  71-74,  163,  277  _ 
Central  nervous  system,  effect  of  thyroi- 
dectomy on,  434 
Cephalopods,  26 
Cereals,  food  value  of,  70-71 
Cerebrospinal  fluid,  225,  226,  227 
Cetacea,  absence  of  salivary  glands  in, 

130 
Chemical  elements,  13-26 
Chemical  potential  energy,  29  ;  conver- 
sion into  different  forms  of  energy, 
35-36 
Children  (see  also  Infants),  food  com- 
pared with  that  of  adults,  70,  82, 
84-85 
Chlorids,  83 
Chlorin,  circulation  of,  20;  in  febrile 

urine,  426-427 
Chlorophyll — 

In  plants  and  animals,  38—40 

Belation  to  iron,  22 
Chocolate,  value  as  food,  124 
Cholalic  acid,  177,  337 
Cholesterin,  80-81,  179 
Cholin,  75-76,  409 
Chondrin,  42 ;  composition,  179 
Chyle,  187-188,  225 
Circulation  of  blood,  5 
Cirrhosis  of  liver,  295 
Citric  acid,  as  food-stuff,  42 
Coagulation  of  blood,  200-205 
Coal,  carbon  as,  14 
Cocoa  bean,  124 
Coffee,  122-124 
Cola  nut,  123 
Collidin,  411 
Colloids,  44-45 
Colostrum,  107 
Colpodella  pugnax,  selection    of  food 

by,  4 

Combustion,  effect  on  organic  life,  18 
Comma  bacillus,  action  of  HCl  on,  142 
Consciousness,  relation  to  space,  2 
Conservation  of  energy,   in  inorganic 
nature,  27-30  ;  law  of,  29 ;  relation 
to  animal  life,  31-34;  to  psychical 
processes,  34,  36-38 


INDEX 


451 


Constipation,  some  causes,  72 

Copper,  circulation  of,  26 
Oxid  of,  colloidal  form,  45 
Compound  of  egg  albumin,  51 

Creatin,  125,  128,  296 ;  synthesis  of,  297 

Creatinin,  125,  128,  297 

Cremation  versus  burial,  18-19 

Crustacea,  copper  in  blood  of,  26 

Crystalline  proteid,  46 

Crystalloids,  46 

Cystein,  327 

Cystin,  327 

Dextrin,  162 

Diabetes,  386-407 
Glycogen  formation  in,  346 
Insipidus,  402 
Pancreatic,  398 
Phloridzin,  346 

Diabetic  coma,  391,  403 
Puncture,  395 

Diamond,  carbon  as,  14 

Diatomacese,  silica  of,  23 

Diet- 
After  thyroidectomy,  438 
Percentage  of  food-stuffs  in  articles 

of,  64-74 
Regulation,  145 

Diffusion  and  vital  processes,  3-4 

Digestion — 
Artificial  pancreatic,  163 
Influence  of  alcohol  on,  121 
Pancreatic — see  Pancreatic  Juice 
Poisonous  products  of,  417 

Diphtheritic  toxin,  413-414,  418 

Diuretics,  effects  of,  319 

Dolium  galea,  133-134 

Duodenal  fistula,  278 

Dyspnea,  on  mountains,  242 

EcK's  fistula,  296 
Egg-albumin,  45 

Copper  compound  of,  51 

Crystallization  of,  52 

Proportion  of  sodium  and  potassium 
in,  98 

Silver  compounds,  51-52 
Eggs— 

Fluorin  in,  24 

Silicic  acid  in,  24 
Elastin,  58-59 
Electric  currents  in  nerve  and  muscle, 

5 
Electrical  discharges  in  the  atmosphere 

formation  of  nitrites  by,  18 
Endothelial  cells — 

Nerve  supply,  228 

Of  capillary  wall,  selective  activity, 
219-221 
Energy,  conservation  of,  27 
Enzymes,  416-418 
Epithelial  cells — 

Of  bile-ducts,  179 

Of  glands,  4,  83-84,  137,  138,  428 

Of  intestine,  in  food  absorption,  3 
Ethereal  sulphates,  325 
Evolution,  theory  of,  salt  in  animals 

explained  by,  101-103 

Fat— 

Formation,  358-369 


Fat — continued 

In   milk  in  different  climates,  107- 
108 

Selection  of,  by  epithelial  cells,  3-5 

Synthesis  of,  361 
Fats- 
Absorption  of,  71,   174,  184-185,  189- 
191 

Action  of  bile  on,  183-184 

As  food-stuffs,  43,  60-74 ;  as  sources  of 
energy,  351 

Conversion  to  sugar,  346 

Emulsification  of,  164-165,  174    • 

Pancreatic  digestion  of,  163-165 
Fatty  acids  in  food,  360 
Feathers,  silicic  acid  in  ash  of,  24 
Fermentation — 
Feces,  79,  80 

Alcoholic,  143,  158-159 

Butyric,  142-143,  158-159,  251,277 

Hydration  always  accompanies,  158- 
159 

In  stomach,  143-144 

Intestinal,  271 

Lactic,  142-143,  158-159 
Ferments,  152,  155-161 

Ammoniacal,  322 

Diastatic,  160 

Heat,  influence  on  activity  of,  160-161 

Isolation,  159 

Organized  and  unorganized,  158-159, 
161 

Pancreatic,  161-171 

Pepsin,  160 

Rennet,  109-110 

Yeast  cells,  155 
Ferrous  oxid,  oxygen  fixed  by,  16 
Fever,  420-427 
Fistula,  composition  of  bile  from,  180- 

181 
Flourin,  circulation  of,  24 
Food- 
Absorption  of— see  Absorption 

Composition,  65-67 
Daily  ingestion  (adults),  113-114 

Digestibility  of  different  kinds,  68-74 

Of  infants,  104-114 

Potential  energy  of,  31 

Selection  of,  by  cells,  3-4 
Food-stuffs — 

Classes  of,  42^3 

Definition  of  term,  41 

Digestibility  of  different,  68-74 

Heat  equivalent  of,  61 

Inorganic,  82-103 

Iron  in,  376 

Organic,  42-81 

Producing  muscular  energy,  63-64 
Formate  of  lime,   decomposition,  156- 

157 
Formic  acid,  157 

GALL-bladder,  composition  of  bile  from, 

180 
Gases — 

Of  alimentary  canal,  276 

Of  blood,  229-280 
Gastric  juice,  130-150 

Antiseptic  action,  131-134,  142 

Artificial,  160-161 

Different  reactions  of,  138-139 


452 


INDEX 


Gastric  juice — continued 

Pathological,  144 

Reflex  secretion  of,  115-116 
Gastric  mucous  membrane — 

Alkaline  reaction  of,  134 

Softening  of,  145 
Gastric  ulcer,  cause  of,  147-148 
Gelatin  and  gelatin-yielding  substances, 

42,  54r-59,  68,  125,  130-131,  177,  288 
Glands — 

Activity  of,  83-84 

Ductless,  428-447 

Epithelial  cells  of,  4 
Globulin,  46-54 
Globulins — 

In  blood  serum,  216 

In  muscle,  217 
Glomeruli,  318 
Glutin,  42 

Glycerin,  in  diabetes,  406  ;    in  fat  for- 
mation, 361 
Glycocholic  acid,  177,  178 
Glycocol,  177 

Glycogen,    formation    of,    342-347;    in 
diabetes,    396;    effect   of  diabetic 
puncture,  395 
Glycosuria,  386-407 
Glycuronie  acid,  259,  390 
Goiter,  431-i33,  444   _ 
Gout,  excretion  of  uric  acid  in,  302 
Grape-sugar — 

Decomposition,  154-155 

Oxidation,  247 
Graphite,  carbon  as,  14 
Guanidin,  298 
Guanin,  77,  314 

Haik,  silicic  acid  in  ash  of,  24 
Heart-burn,  144 
Hematin,  fate  of,  338 
Hematogen,  375 
Hematoporphyrin,  338 
Hemoglobin,  21-22 

Amount  in  blood,  206-207,  210-215 

Combination  with  oxygen,  141 

Crystals,  49-51 
Hemoglobinuria,  339 
Heat — 

As  source  of  motion,  29-31 

Animal,  source  of,  31-34 

Diminished  loss  of,  in  fever,  422-423 

Effect  on  ferments,  153-161 

Formation  in  decomposition  of  carbo- 
hydrates, 346 

Produced  by  work,  28-29,  31,  35 
Heat-equivalents  of  food-stuffs,  61-62 
Heat-regulation,   effect  of  alcohol  on, 

117-118 
Hippuric  acid,  256,  259,  281-287 
Human  milk — 

Analysis  of,  104 

Composition  of,  104-109 
Hydrobilirubin,  323 
Hydrocele  fluid,  226 
Hydrochloric  acid — 

A  remedy  in  dyspepsia,  144 

Action,  antiseptic,  131-132;  possible 
digestive,  130-131 

Avidity  of,  136 

Formation  from  blood,  134-137,  139 

Liberation  of,  135-139 


Hydrogen — 

Circulation  of,  14 

Formation  of,  251 

In  alimentary  canal,  277 

Peroxid  of,  154 
Hydrolytic  ferments,  416-418 
Hypoxanthin,  77,  313 ;  in  birds,  309 

Immunity,  421 
Indian  cobra,  toxin  of,  418 
Indigo,  in  urine,  324 
Indol,  256 ;  fate  of,  324 
Infants,  food  of,  104-114 
Infection,  408-419 

Inorganic  salts,  role  of,  in  adult  organ- 
ism, 86-90 
Inosit,  402  _ 
Insects,  sodium  in,  102 
Internal  sense,  1-2,  6,  9 
Intestinal  juice,  functions  of,  173-176 

Obstruction,   aromatic    sulphates  in, 
325 

Parasites,  respiration  of,  353 

Wall,  tension  of  COj  in,  268 
Intestine — 

Epithelial  cells  of,  3-4 

Excretion  of  iron  by,  373 

Fermentation  in,  271 

Gases  of,  276,  278 

Peristalsis  of,  influence  of  food,  71-73 
Inulin,  utilization  by  diabetics,  393 
Invertebrates,  sodium  in,  102 
Invertin,  156 
lodin — 

Circulation  of,  23-24 

In  thyroid  gland,  439-440 
Iodoform,  440,  441 
lodothyrin,  440,  441 
Iron,  370-385 

Absorption  of  inorganic,  371 

Amount  in  body,  370 

Circulation  of,  21-22 

Excretion  of,  373 

In  young  animals,  378 

Of  liver,  342 

Oxidation  of,  254 
Iron,  oxid  of,  colloid  form,  44-45 

Jaundice,  pathology  of,  339 
Jequirity  seed,  416 

Keratin,  58 
Kidneys — 

Extirpation  of,  293,  309 

Functions  of,  316-333 

Hippuric  acid  formed  in,  285 

Overworked  by  excessive   salt  diet, 
100 

Pathogenic  bacilli  in,  426 
Kinetic  energy — 

Conversion  into  other  forms  of  energy, 
27-29;  35-36 

Liberation  by  chemical  processes,  153 

Of  sunlight,  29-31 
Koprosterin,  80-81 

Lactic  acid- 
Excretion  after  extirpation  of  liver, 

311 
Formation,  355 
From  sugar,  390 


INDEX 


453 


Lactic  acid — continued 

In  diabetes,  406 

Of  urine,  331 
Lerulose,  utilization  of,  392 
Lathrodectes  tredecimguttatus,  416 
Lecithin,  75-77,  179 
Leguminosse,  17-18,  70 
Leukemia,  uric  acid  in,  307 
Leucin,  167 
Leucocytes — 

Blood  coagulation  and,  202-204 

Digestion  and,  197-198 

Function  of,  222-223 

Increase  of,  in  fevers,  425 
Lieberkühn's  glands,  172,  175 
Lime — 

In  milk  of  different  mammals,  106 

Necessity  for,  in  children's  food,  84r- 
85 
Lime,  formate  of,  decomposition,  156- 

157 
Limestone,  16 
Liver — 

Extirpation  of,  296 ;  in  birds,  310 

Glycogen  formation  in,  342 

Iron  in,  342 

Metabolism  in,  334-347 

Urea  formation  in,  294 
Lung  catheter,  265 
Lungs,  tension  of  gases  in,  266 
Lymph,  21&-228 

Cells,  and  digestion,  197-198 

CO2  in,  267 

Composition  of,  225-228 

Formation  of,  219 

Functions  of,  222-223 

Glands,  function  of,  223 

Rate  of  flow,  219 

Relation  to  cell  nourishment,  219-221 

Spaces,  uses  of,  222 
Lysatin,  298 
Lysin,  289 

Magnesia  compound  of  globulin,  46- 

49 
Magnesium,  circulation  of,  20 
Maize,  silicic  acid  in  ash  of,  23 
Malic  acid,  42 
Malpighian  bodies,  318 
Maltose,  162 

Mammals,  composition  of  milk  of  dif- 
ferent, 104-109 
Manganese,  circulation  of,  25 
Marsh-gas,  277 
Mass  influence,  136,  240,  263 
Meat,  nutrient  value,  68 
Meat  diet,  and  need  for  salt,  90-100 

Extracts,  food  value  of,  124-128 
Mechanism,  as  an  explanation  of  vital 

processes,  1-12 
Metabolism — 

During   work,    349 ;    during  mental 
work,  36-38 

In  fever,  421-424 

Influence  of  alcohol  on,  120 ;  of  thyroid 
gland  on,  439,  442 

In  liver,  334-337 

Nitrogenous  end-products  of,  281 

Products  of  bacterial,  408-419 
Methylamin,  411 
Methylguanidin,  410 


Milk- 
As  food,  65-70,  104-114 

Ash  of,  82-83,  105,  376 

Cholesterin  in,  80 

Composition,  65-67,  82,  104-114 

Inorganic  salts  in,  81-86,  97,  98,  105 

Iron  in,  376 

Lecithin  in,  77 

Nucleins  in,  79  and  n.  2 
Milk  diet,  bad  effects  of,  72,  383 
Millon's  reaction,  56,  n.  2 
Molluscs,  secretion  of,  133-134 
Monotropa,  39 
Motion,  different  forms  of,  27;   origin 

of,  29-30 
Mucin,  179 
Mucoid,  179-180 
Muscarin,  76 
Muscles — 

Action  of  creatin  and  Creatinin  on, 
128 

Functions  of,  how  far  explicable,  5 

Destruction  of  sugar  in,  394 

Gases  of,  350 

Glycogen  in,  343 

Metabolism  of,  294  _ 

Skeletal,  in  starvation,  216 

Storage  of  proteid  in,  217 

Urea  m,  297 
Muscular  energy,  source  of,  63,  64,  348- 

357 
Myxedema,  430 

Nekve  functions,  how  far  explicable,  5 
Nervous  system,  effect  of  thyroidectomy 

on,  439 
Neuridin,  410 
Neurin,  409 
Nitroglycerin,  153 
Nitrogen — 

Circulation  of,  17-18 

Elimination,   63,    120-121;   in  work, 
349 ;  in  fever,  424-425 

In  feces,  69 

In  intestines,  276 

In  respiration,  237 
Nitrogen,  iodid  of,  154 

Trichlorid,  153,  154 
Nitrogenous  end-products,  281 

Equilibrium,  maintenance  of,  193 

Food,  heat-equivalent  of,  in  the  body 
and  calorimeter,  63 
Nucleic  acid,  78-79 
Nucleins,  77-80,  374 

Obesity,  368 
Organic  acids — 

As  food-stuffs,  41-42 

Avidity_  of,  136 

Formation  of,  in  the  blood  in  fevers, 
425 
Organic  compounds  of  iron,  373 
Ornithin,  287,  298 
Ornithuric  acid,  287 
Osmosis  and  vital  processes,  3-4 
Ossein,  42 

Ovaries,  iodin  in,  25 
Ovurp,  development  from,  4 
Oxalic  acid — 

Fate  of,  in  the  body,  332 

In  urine,  331 


454 


INDEX 


Oxaluric  acid,  305 
Oxidation — 

In  blood,  243 

In  diabetes,  389 

In  tissues,  244 

Mechanism  of,  247 
Oxidizing  property  of  tissues,  248 
Oxybutyric  acid,  312,  391 
Oxygen- 
Absorption  of,  238_ 

Balance  of  carbonic  acid  and,  14-17 

Carriers,  253 

Circulation  of,  14-17 

In  respiration,  237-260 

In  saliva,  246 

Inspired,  as  a  food-stuff,  42 

Intake  in  fevers,  422 

Eequirements   of  different    animals, 
353 
Oxyhemoglobin,  240;    dissociation    of, 

242 
Ozone,  248 
Pancreas,   152,  166 ;   extirpation  of, 

398 
Pancreatic  diabetes,  398 

Juice,    151-152,    161-171 ;    action    on 
carbohydrates,   162-163;    fats,  163- 
166,  184-185;  proteids,  166-171 
Para  nut,  crystalloids,  46 
Parabanic  acid,  305 
Parasites,  metabolism  of,  253 
Pepsin,  160-161 
Peptones — 

Different  forms  of,  169-170 

Fate  of,  197-199 

Formation  of,  166-169 

In  urine,  199 

Nature  of,  171,  n. 

Regeneration  of,  194-197 
Pericardial  fluid,  226 
Peritoneal  transudation,  226 
Perspirahile  retentum,  272 
Perspiration,  275 
Phenol,  fate  of,  257 
Phloridzin  diabetes,  346,  387 
Phosphates  of  blood  plasma,  263,  264 
Phosphoric  acid — 

In  milk  of  different  mammals,  106 

In  plant  life,  20 
Phosphorus — 

Circulation  of,  20 

Compounds,  75-80 

Influence  of  nitrogen  excretionon,  121 

Oxidation  of,  255 

Poisoning,  426 ;  assimilation  of  sugar 
in,  398 
Pigments  rejected  by  epithelial  cells, 
3-4 

Bile,  178  ;  origin  of,  336 

Urinary,  323 
Pinnipedia,  salivary  glands  in,  130 
Pituitary  body,  446-447 ;  iodin  in,  25 
Plants — 

Contrast  between  animals  and,  38-40 ; 
interdependence,  14,  16 

Iron  in,  22 

Silicic  acid  in,  23 

Sodium  in,  102 
Pleural  fluid,  226 

Poisons — see  Arsenic,   Bacteria,   Phos- 
phorus 


Polyuria  in  diabetes,  402 
Potassium,  circulation  of,  20 
Potassium  chlorate,  dissociation  of,  154 
Potassium  salts — 

Action  of,  126-127 

Distribution  over  the  surface  of  the 
globe,  101 

In  food,  83-103,  105 

Injection  of,  into  blood,  127 
Potatoes — 

Food  value  of,  68-70 

Potassium  salts  in,  92,  97 
Potential  energy — 

Chemical,  29 

Conversion  into  kinetic  energy,  27-29, 
35-36 

Of  plants,  30 
Proteid — 

Absorption,  68-71,  191-199 

Amount  in  different  food-stuffs,  65-68 

Classification  and  properties,  43-45 

Conversion    into    peptones,   168-169; 
reconversion  of  peptone,  197-199 

Crystallization  of,  46-54 

Decomposition  of,  288 

Digestion  of,  68-70 

Disintegration  of,  in  fever,  424-425 

Effect  on  glycogen,  345 

Fat  formation  from,  363 

Gastric  digestion  of,  130-131 

Importance  as  food-stuffs,  43 ;  in  vital 
processes,  64 

In  blood  serum,  207,  216 

In  Ij^mph,  228 

In  milk  of  mammals,  105-106 

Molecular  weight  of,  47 

Of  bacterial  poisons,  413-415 

Pancreatic  digestion  of,  166-171 

Source  of  energy,  351 
Ptomains,  action  of,  412-413 
Pulmonary  catheter,  265 
Putrefaction,  alkaloids  of  bacterial,  409- 

413 
Pylorus — 

Alkaline  secretion  of,  138 

Resection  of,  139 
Pyrogallol,  oxidation  of,  250 

Quinine,  action  on  cells,  287 

Effect  on  formation  of  uric  acid,  308 
Quotient,  respiratory,  270 

Rattlesnake,  poison  of,  418 

Red  marrow,  changes  after  extirpation 

of  spleen,  231-232 
Reducing  powers  of  tissues,  341 
Reflex  secretion  of  gastric  juice,  115-116 
Rennet,  action  on  milk,  109-110 
Respiration,  229-280 ;  at  low  pressures, 
241 
Cutaneous,  271 
Respiratory  exchange,  270 ;  in  diabet- 
ics, 390 
Respiratory  foods,  63 

Quotient,  270 
Rhizopods,  method  of  taking  up  food,  3 
Rice — 
Potassium  salts  in,  96-97 
Suitability  of,  in  renal  disease,  100- 
101 
Rickets,  85 


INDEX 


455 


Rock  crystal,  46 
Ruby,  46 

Saliva,  129-130,  246 

Salmon,  synthesis  of  lecithins  and  nu- 

cleins  in,  79-80 
Salt  frog,  246 

Saltpeter,  formation  of,  252 
Secretions,  cell  functions  in  process  of,  4 
Serum  of  blood,  200,  206-211,  213-215, 
216,  225 

Salts  of,  262 
Serum-albumin,  45 
Silicic  acid,  struggle  with  carbonic  acid, 

15-16 ;  colloid  form,  44 
Silicon,  occurrence,  23-24 
Silver  compounds  of  egg  albumin,  51- 

52 
Skin,  exchanges  through,  274 
Snake  poison,  416 
Soaps,  formation  in  digestion,  164^165  ; 

in  bile,  179 ;  in  blood  serum,  216 
Sodium — 

Circulation  of,  20 

Distribution  over  the  surface  of  the 
globe,  101 

In  blood,  208 

In  food,  83-103 
Sodium  Chlorid,  90-103 
Sodium  compound  of  globulin,  47 
Specular  iron  ore,  46 
Spermatozoon — 

Hereditary  transmission  through,  8 

Nucleic  acid  from,  79 
Spiders,  poisons  of,  416 
Spleen — 

Extirpation,  229-234 

Functions,  231,  235-236 

Influence  on  uric  acid,  307,  308 

lodin  in,  25 

Peptones  in,  197 
Staphylococcus  toxin,  418 
Starch,  digestion  of,  156,  162-163 
Starvation,  effects  of,  392 
Sterilization  of  milk,  110 
Stomach — 

Functions  of,  140-142,  148-150 

Extirpation  of,  140-141 

Self-digestion  of,  145-148 
Streptococcus  toxin,  415 
Sugar — 

Absorption  of,  188-189 

Assimilation    in   phosphorus  poison- 
ing, 398 

Destruction  in  muscles,  394 

Formation  from  fats,  346 

In  blood,  origin  of,  188-189 

In  normal  urine,  331 

Levorotatory,  in  diabetes,  387 
Sulphates,  aromatic,  256,  325 
Sulphocyanic  acid,  330 
Sulphur — 

As  oxidizing  agent,  21 

Circulation  of,  20 

In  proteid,  47-53 

Of  hemoglobin,  239 
Sulphuretted  hydrogen,  144,  278 
Sulphuric  acid — 

Action  after  removal  of  basic  salts 
from  food,  87-89 

Avidity  of,  136 


Sulphuric  acid — continued 

Decomposition  product  from  proteid, 
87 

Elimination  in  fever,  422 

In  saliva  of  molluscs,  134 
Sunlight  a  source  of  energy,  29-31,  35 
Suprarenal  capsules,  428-430 
Symbionta,  39  n.  4 
Synthetic  processes  in  the  body,  283 

Tartaric  acid,  as  a  food-stuff,  42 
Taurin   177-178,  327  ;  fate  of,  329 
Taurocholic  acid,  177,  178 
Tea,  122-124 
Teeth,  fluorin  in,  24 
Temperature — 

After  throidectomy,  436-437 

Alcohol,  effect  on,  118 

In  fever,  420-424 

Its  influence  on  vital  processes,  64 
Tension  of  CO2  in  blood,  262 ;  in  lungs, 

266 
Tetanus  toxin,  412-413,  414-415,  418 
Tetany,  435,  436 
Theobromin,  124 
Thiosulphuric  acid,  330 
Thrombosis,  202 
Thymus,  25,  236 
Thyroid  gland — 

Administration  of,  439,  443,  444 

Connection  with  pituitary  body,  446- 
447;  with  sexual  functions,  444- 
446 

Extirjjation,  431-438 

Functions,  442 

lodin  in,  25 

Isolation  of  active  principle,  439-441 

Subcutaneous  injection  of  the  juice, 
439 

Transplantation,  438,  442-443 
Tissue,  non-digestion  of  living,  145-147 

Change  and  food,  64-65 

Development,  relation  of  thyroid  to, 
434 
Tissues,  reducing  power  of,  251 
Toxalbumins,  416-419 
Toxins,  412-413 

Transudations,  analyses  of,  225-226 
Trimethyl  -  vinyl-ammonium-hydroxid, 

409 
Tubercle  bacillus,   142,   420 ;   products 

of,  415,  418 
Typhoid  bacillus,  421 
Typhus  toxin,  418 
Tyrosin,  56  n.  2,  57,  167 

Urea— 

Constitution  of,  288 

Excretion  increased  by  rise  of  tem- 
perature, 424 

Formation  from  ammonia,  293 
Uric  acid,  299 

Formula  of,  306 

Of  birds,  309 

Oxidation  of,  304 

Solubility  in  urine,  322 

Synthesis  of,  303 
Urinary  sediments,  301 
Urine — 

Abnormal  acids  in,  391 

Ammonia  of,  295 


456 


INDEX 


Urine — continued 

Analysis  of,  320 

Composition  of,  316-333 

Cystin  of,  327 

Hippuric  acid  in,  282 

Indigo  in,  324 

In  fever,  426 

Iron  in,  22 

Peptones  in,  199 

Pigments  in,  323 

Sugar  in,  387 

Uric  acid  of,  300 
Urobilin,  323;  formation  of,  339;  pro- 
duction in  fevers,  425 

Vampyrella  Spirogyrce,  selection  of  food 
by,  3 

Vegetable  diet  and  need  for  salt,  91-100 

Vegetables,  nutrient  value  of,  68-74 

Vegetarianism,  70-71 

Vertebrates,  sodium  in,  102 

Vital  phenomena — 
Mechanical  explanation  of,  1-12 
Psychological  explanation  of,  6,  9-10 


Vitalism,  1-2,  10-11 
Vorticellse,  40 

Water— 
Absorption  from  the  stomach,  148 
Influence  of  mass,  136 
Necessity  of,  in  the  organism,  86 
Proportion  by  weight  of  oxygen  in 
total  amount  of,  14 

Woody  fiber,  in  digestion,  71-74 

Work- 
Definition  of,  27 
Influence  on  fat  formation,  368 
Source  of,  348 

Xanthin,  77,  308 
Bases,  313 

Yeast,  nucleic  acid  from,  78  ;  nuclein 

from,  78 
Yeast  cells,  155 
Yolkofegg,  85,  98 


INDEX  OF  AUTHORS 


Abderhalden,  E.,  analyses  of  blood, 

209 
Abeles,  M. — 
Glycogen,  343,  396 
Sugar  in  urine,  331 
Abelmann,  M.,  fat  absorption  after  ex- 
tirpation of  pancreas,  166 
Abelous,  E.,  extirpation  of  suprarenals, 

429  ;  of  thymus,  236 
Abrahams,  E..,  administration  of  thy- 
roid, 444 
Addision,    T,,  disease  of  suprarenals, 

428 
Addison,  W.,  fibrin,  202 
Adlerskron,  B.  v.,  chlorin    in  cereals, 

84  n. 
Aeby,  glycogen,  345 
Afonassiew,  N.,  reducing  substances  in 

corpuscles,  247 
Albertoni,  acetone,  403 
Aldehoflf,  G.— 
Functions  of  stomach,  148 
Glycogen  of  muscles,  344 
Altmann,  nucleic  acid,  78 
Anderson,  metabolism  in  fever,  424 
Andre,   A.,  heat-equivalents    of    food- 
stuffs, 61-62 
Andreasch,  absorption  of  caffein,  123 
Augerer,  O.,  administration  of  thyroid, 

444 
Anrep,  B.  v.,  absorption  in  dog's  stom- 
ach, 148 
Anstie,  excretion  of  alcohol,  117 
Argutinsky,  P.,  sweat,  275 
Arnold,  J. — 

Functions  of  bile,  183 
Pituitary  body,  447 
Amschinck,  glycerin,  362 
Aronsohn,  influence  of  nervous  system 

on  fevers,  423 
Aronstein,    solutions  of    albumin  free 

from  salts,  45  and  n.  4 
Arthus,  M. — 
Blood  coagulation,  205 
Ferments,  109,  n.  4 ;  161 
Aschaffenburg,  G.,  alcohol,  118 
Astachewsky,  formation  of  lactic  acid, 

355 
Aubert — 
Cutaneous  respiration,  272 
Frog  without  oxygen,  354 
Temperature  and  bacteria,  420 
Auerbach,  phenol,  257 
Autokratow,  P.  M.,  extirpation  of  thy- 
roid, 435 
Avaldt,  synthesis  of  fats,  361 

Baas,  acidity  of  gastric  juice,  325 
Baer,  A.,  alcohol,  119 


Baeyer,  v. — 

Cholin,  75 

Indigo,  324 

Neurin,  409 

Uric  acid,  302 
Baginsky,  A. — 

Acetonuria,  391 

Eickets,  85,  n.  1 

Sterilization  of  milk,  110 
Balfour,  J.  M.,  bile  fistula,  176 
Barbieri,  decomposition  of  proteids,  288 
Bard,  temperature  and  bacteria,  420 
Barral,  salt  food  for  animals,  99 
Bartels — 

Leukemia,  307 

Urea  excretion  and  temperature,  424 

Uric  acid,  301 
Barth,  M  — 

Invertin,  156 

Isolation  of  ferments,  160 
Bartholini,  lymph,  220  n.  1 
Bary,  W.  de,  bacteria  in  the  stomach, 

143 
Bauer,  J. — 

Absorption  of  proteid,  192 

Alcohol,  121 

Phosphorus  poisoning,  363 
Baum,   P.,  influence  of  food    on    the 

composition  of  milk,  112 
Baumann — 

Aromatic  amido-acids,  257 

Cystin,  327 

Indigo,  324 

Intestinal  obstruction,  325 

lodin,    25;    in    thyroid    gland,    439, 
440,  441 

Methyl-guanidin,  410 

Nitrous  acid,  formation  of,  250 

Oxidation,  251 
Baumert,  intestines  offish,  276 
Baumgarten,  leucocytes,  223 
ßaumgärtner,  oxidation  in  egg,  244 
Bayer,  H.,  bile  acids,  177 
Beadles,  administration  of  thyroid,  444 
Beale,  L.,  fibrin,  202 
Beaumont,  W.,  gastric  digestion,  151 
Bechamp,  J.,  peptone,  171 
Beneke,  crystinuria,  329 
Berdez,  alcohol,  121 
Bergmann,  E.  v. — 

Bacterial  poisons,  409 

Bile  pigments,  339 

Transfusion  of  blood,  205 
Bernard,  C. — 

Carbonic  oxid,  240 

Diabetes,  386 ;  diabetic  puncture,  395 

Digestion  of  living  tissue,  146 

Glycogen,   343;  of  muscle,  381 

Pancreatic  juice,  164 


457 


458 


INDEX    OF    AUTHORS 


Bernard — continued 

Pvrogallol,  255 
Bert,  P.— 

Effect  of  low  pressure,  241 

Poisonous  effects  of  CO2,  268 
Berthelot — 

Electrical  discharges,  18 

Heat-equivalents  of  food-stuffs,  61-62 
Berlinerblau,  lactic  acid,  355 
Berzelius,  hippuric  acid,  283 
Bezold,  A.  v.,  salt,  98 
Bidder — 

Absorption  of  iron,  372 

Bile  functions,  183 ;   biliary  fistula, 
176 

Gastric  juice,  130,  132 

Pancreatic  juice,  165 

Saliva,    amount    in    24    hours,    129 ; 
secretion  of  dog's,  149 

Starvation,  216 
Biedert,  Ph.,  artificial  feeding,  108,  112 
Bienstock,  B.,  feces,  143 
Bikfalvi,  alcohol,  121 
Billard,  excision  of  thymus  in  frog,  236 
Billroth,  excision  of  goiter,  432 
Binz,  C— 

Alcohol,  117,  118 

Quinine,  287 
Bircher,  transplantation  of  thyroid,  442 
Birk,  L.,  blood  coagulation,  203 
Bischoff,  E  — 

Meat  extract,  126 

Sulphur  of  urine,  326 
Bizzozero,  J.,  blood  coagulation,  204 
Bleibtreu,  administration    of  thyroid, 

443 
Bleue,  A.  M.— 

Colloid  carbohydrates  in  portal  blood, 
163 

Sugar  in  blood-corpuscles,  188,  01.  2 
Blondlot,  bile  functions,  183 ;    biliary 

fistula,  176 
Blumenreich,  L. — 

Extirpation  of  thyroids,  435 

Pituitary  body,  446 
Boas,  J.,  H2S  in  the  stomach,  144 
Bock,  diabetes,  388 

Bodländer,  G.,  excretion  of  alcohol,  117 
Boeck,  alcohol,  121 

Boedeker,  analysis  of  secretion  of  mol- 
luscs, 133-134 
Boehm — 

Cholin,  76 

Glycogen,  365 ;  of  muscles,  344 
Boettcher,  A.,  hemoglobin  crystals,  49, 

TO.  2  _ 

Bohland,   elimination  of  ammonia  in 

fever,  425 
Böhm,  R.,  glycogen,  343 
Boinet,  E.,  extirpation  of  suprarenals, 

_  429 
Bojanus,  N.,  blood  coagulation,  203 
Bökay,  S.— 
Lecithins,  77 
Nuclein,  79,  n.  3 
Bonardi,  E.,  febrile  urine,  426 
Bondzynski— 
Albumin  crystals  from  white  of  egg, 

52-53 
Koprosterin,  80 
Sulphur  of  urine,  326 


Bossar,  decomposition  of  proteids,  288 
Bouchard,  febrile  urine,  426 
Bourgeois,  decomposition  of  proteids, 

288 
Bourneville,  pituitary  body,  446 
Boussingault,  iron  and  chlorophyll  in 

plants,  22 
Bramwell,   B.,   crystallization  of  pro- 
teids in  urine,  53 
Brandt,  K.,  chlorophyll  granules,  39 
Braunschweig,  v.,  thymus,  236 
Brefeld,  anaerobic  fermentation,  158 
Breisacher,  L.,  thyroidectomy,  438 
Bricon,  pituitary  body,  446 
Brieger,  L. — 

Bacteria,  143 ;  bacterial  poisons,  409- 
411,  414 

Feces,  143 

Febrile  urine,  426 

Indigo,  324 

Tetanin,  412 
Brown,  H.  T.,  digestion  of  starch,  163 
Brown-Sequard,  extirpation  of  supra- 
renals, 428-429 
Brücke — 

Blood,  201 

Conversion  of  proteid  to  peptone,  167 

Digestion  of  starch,  162 

Emulsifying  action  of  alkalies,  165 

Glycogen,  343 

Isolation  of  ferments,  159 

Reaction    of   gastric    mucous    mem- 
brane, 134 
Brunner,  T.,  changes  in  composition  of 

milk,  107 
Bruns,  administration  of  thyroid,  443, 

444  _ 
Buchheim,  fate  of  ammonia  salts,  291 
Büchner,  E.,  fermentation,  155 
Büchner,  H.,  natural  immunity,  419 
Büchner,  W.,  alcohol,  121 
Bujwid,  0.,  tubercle  toxin,  415 
Bunge,  G. — 

Analyses  of  blood,  quantitative,  207 ; 
comparative,  of  ash,  82-83,  105 

Composition  of  milk,  107 

Dog's  milk,  220 

Effect  of  potassium  salts  on  gastric 
mucous  membrane,  101 

Hippuric  acid,  284 

Inorganic  salts,  88 

Intestinal  parasites,  353 

Life  without  oxygen,  244 

Meat  extract,  126 

Nuclein, 78 

Organic  iron,  373 

Uric  acid,  302 
Bumm,  temperature  and  bacteria,  420 
Bunsen,  gas  analysis,  229 
Bun tzen,  vegetable  diet,  71 
Burckhardt,  blood  in  starvation,  216- 

217 
Busch,  emptying  of  the  stomach,  151 

Cahn,  a.,  acids  in  the  stomach,  144 
Cannon,  gastric  digestion,  129 
Cantani,  diabetes,  386 
Carvallo,  J.,  extirpation  of  stomach, 

140 
Cash,  Th.,  absorption  of  fats,  175 
I  Catou,  R.,  pituitary  body,  447 


INDEX    OF    AUTHORS 


459 


Cattani,' bacterial  poisons,  411,  413,  414, 

419 
Caussade,  G.,  suprarenal  capsules,  430 
Cazeneuve,  P. — 

Ammoniaeal  decomposition,  322 

Phosphorus  poisoning,  363 

Sterilization  of  milk,  110 
Cech,  urea  in  birds,  309 
Chittenden,  R.  S.— 

Composition  of  elastin,  58 

Digestion  of  proteids,  167,  171 
Chossat,  starvation,  216 
Chrzonsczewski,  indigo  injection,  318 
Cienkowski,     L.,    [food    selection     by 

amebse,  3-4 
Cleve,  cholalic  acid,  177 
Cloetta,  M.,  assimilation  of  iron,  380 
Coen,  E.,  secretion  of  milk,  113 
Cohnheim — 

Isolation  of  ferments,  159 

Salt-frog,  246 
Cohnstein,  lymph,  218 
Coindet,  iodin  administration  in  goiter, 

440 
Colasanti,  metabolism  in  fever,  422 
Collis,  A.  J.,  pituitary  body,  447 
Connini,  pituitary  body,  447 
Copeman,  biliary  fistula,  176 
Coranda,  excretion  of  ammonia,  292 
Cordua,  H.,  bUirubin,_388 
Corvisart,  pancreatic  juice,  166 
Costanzo,    administration    of    thyroid, 

443 
Coutaret,  L.,  digestion  of  starch,  162 
Cramer,  sweat,  275 
Cristiani,  H. — 

Accessory  thyroids,  435,  n.  5 ;  436 

Extirpation  of  thyroid,  437 
Czerny,  V. — 

Absorption  of  proteids,  192 

Extirpation  of  dog's  stomach,  140 

Dallemagne,  M.,  pituitary  body,  447 
Danilewsky — 

Attempt  to  isolate  three  pancreatic 
ferments,  161 

Comparison    of    heat-equivalents    of 
gelatin  and  proteid,  56,  171 

Globulin  in  muscles,  217 

Heat-equivalents  of  food-stuiFs,  60-62 

Isolation  of  ferments,  159 

Proteid  in  muscles,  217 
Dastre,  A. — 

Extirpation  of  spleen,  230 

Fat  absorption,  184-185 
Debray,  decomposition  of  formic  acid, 

157 
Deichmüller,  febrile  urine,  425 
Demant,  intestinal  juice,  173-174 
Demesmay,  salt  food  for  animals,  99 
Demme,  action  of  alcohol,  122 
Dennig,  administration  of  thyroid,  443 
Desaive,  salt  food  for  animals,  99 
Despretz,  source  of  animal  heat,  33 
Dessaignes,  synthesis  of  hippuric  acid, 

282 
Deville,  decomposition  of  formic  acid, 

157 
Diakonow,  lecithin,  75,  76 
Ditmar,    C.    v.,    salt    and    meat    diet, 

93-94 


Dominicis,  X.  de,  extirpation  of  supra- 

renals,  429 
Donath,  E.,  invertin,  156 
Donders,  carbonic  acid,  263 
Dragendorft^— 

Absorption  of  caffein,  123-124 

Bile  acids,  336 
Drechsel,  E. — 

Active  principle  of  thyroid,  441 

Diamido-acids,  289 

Iodin,  25 

Lysatin,  298 

Organic  silicon  compound  in  birds' 
feathers,  24 

Ornithin,  287 

Proteids,  45,  47 

Urea,  origin  from  carbonate  of  am- 
monia, 292 
Dreser,  H.,  alcohol,  117 
Drosdofif,  analyses  of  portal  and  hepatic 

blood,  335 
Dulong,  source  of  animal  heat,  33 
Dupre,  excretion  of  alcohol,  117 

Ebbstein— 

Cystin  in  urine,  329 

Gout,  302 

Urinary  calculi,  321 
Eberth,  J.  C,  origin  of  thrombi,  202 
Eck,  fistula  of,  296 
Edkins,  pancreatic  ferment,  161 
Edmunds,  A.,  rennet  ferment,  109 
Ehrlich— 

Reducing  substances,  251 

Reduction  in  tissues,  341 
Ehrenmeyer,  lactic  acids,  312 
Eichhorst,  absorption  of  proteids,  192 
Eiselsberg,  A.  v. — 

Excision  of  goiter,  433 

Thyroid  gland,  401,  444;  extirpation 
of,  435,  437 ;  transplantation  of,  438- 
439 
Elsässer,  softening  of  the  stomach,  145 
Emelianow,  P.,  extirpation  of  spleen, 

229,  230,  232 
Emich,  antiseptic    properties  of  bile, 

185 
Emminghaus,  lymph-formation,  318 
Engelmann — 

Arcellse,  6-7 

Chlorophyll,  39-40 
Entz,  G.,  chlorophyll-granules,  39 
Erman,  intestinal  gases,  276 
Etzinger,  J.,  digestion  of  cartilage  and 

bone,  58 ;  of  elastin,  59 
Ewald,  C.   A.,  administration  of  thy- 
roid, 443,  444 
Ewald,  J.  R.— 

Extirpation  of  thyroid,  435,  437 

Pituitary  body,  446 

Falk,  tubercle  bacillus,  142 

Favre,   heat-equivalents  of  food-stuffs, 

61-62 
Fechner,  on  sensations,  37 
Feder,  fate  of  ammonia  in  the  body, 

291 
Feer,  E.,  infant  feeding,  108,  111,  112 
Fehr,  C,  extirpation  of  salivary  glands, 

130 
Feiertag,  H.,  blood  coagulation,  203 


460 


INDEX   OF   AUTHORS 


Fick— 

Artificial  gastric  juice,  160 

Ascent  of  Faulhorn,  348 
Filehne,  action  of  theobromin,  124 
Filippi,  F.  de,  extirpation  of  stomach, 

140 
Finger,  temperature  and  bacteria,  420 
Finkler,  D.,  metabolism  in  fever,  422 
Finn,  B.,  glycogen,  345 
Fischer,  E.,  314 

Caffein,  123 

Uric  acid,  302 ;  reduction  of,  314 
Fischer,  J.,  thyroid  gland,  445 
Flavard,  sulphur  of  urine,  326 
Flaum,  M.,  artificial  gastric  juice,  160 
Fleischer — 

Bile  acids,  336 

Leukemia,  307 
Flügge,  analysis  of  portal  blood,  335 
Foa,  P.,  suprarenal  capsules,  430 
Fokker,  A.  P.,  alcohol,  120 
Forster — 

Albuminuria,  317 

Nitrogenous  excretion,  193 

Role  of  inorganic  salts  in  the  adult 
organism,  87 
Frank,  action  of  HCl  on  certain  bac- 
teria, 142 
Fraenkel,  A. — 

Anaerobic  fermentation,  158 

Influence  of  rarefied  air,  241 

Temperature  and  bacteria,  420 

Metabolism  in  fever,  422 
Fraenkel,  C,  bacterial  poisons,  414 
Fraenkel,  S. — 

Active  principle  of  thyroid  gland,  441 

Suprarenal  capsules,  430 
Frankland — 

Analysis  of  porpoise  milk,  104,  105 

Heat-equivalents  of  food-stufls,  60-62 
Fredericq — 

Blood  coagulation,  203 

Copper  in  blood,  26 

Digestion  in  higher  and  lower  ani- 
mals, 152 

Salivary  glands  of  the  octopus,  134 
Frerichs — 

Composition  of  bile,  180 

Diabetes,  386 

Freudenreich,  E.  v.,  bacteria  in  milk, 
110 
Freund,  milk  diet,  383 
Freund,  H.  W.,  thyroid  gland,  445 
Frey,  M.  v. — 

Emulsifying  action  of  alkalies,  165 

Gases  of  muscles,  350 

Lactic  acid  in  muscle,  355 
Friedel,  C,  silicon  compounds,  23 
Friedländer,  efiects  of  CO2,  268 
Frommel,  secretion  of  milk,  113 
Fubini,  respiration  in  frogs,  271 
Funke,  C,  perspiration,  275 
Fiirbringer — 

Metabolism  in  fever,  422 

Oxalic  acid,  331 
Fürer,  C,  alcohol,  118 
Fürst,  L.,  sterilization  of  milk,  110 
Fürth,  O.  v.,  suprarenal  capsules,  430 

Gad,  J.,  emulsifying  action  of  alkalies, 
165 


Gaehtgens,  C,  diabetes,  392 
Gaglio,  G.— 

Lactic  acid,  355 

Oxalic  acid,  fate  of,  332 
Gara,  G.,  thyroid  administration,  444 
Garnier,  P.,  action  of  alcohol,  122 
Garrod — 

Gout,  302 

Urobilin,  323 
Gaule,  A.  L.,  splenic  functions,  235 
Gaule,  J. — 

Absorption  of  iron,  372 

Carbonic  acid,  263 
Gautier — 

Bacterial  poisons,  409 

Xanthin,  314 
Gavarret,  source  of  animal  heat,  34 
Geddes,  P.,  chlorophyll  granules,  39 
George,  W.  H.,  administration  of  thy- 
roid, 444 
Georgiewsky,  K.,  influence  of  thyroid 

on  metabolism,  439 
Geppert,  J. — 

Alcohol,  121 

CO2  in  febrile  blood,  425 

Gas  analysis,  237 

Influence  of  rarefied  air,  241 
Gergens,  methyl-guanidin,  410 
Gernet,  administration  of  thyroid,  444 
Giacosa — 

Aromatic  hydrocarbons,  258 

Oxidation,  250 

Spleen,  308 
Gilson,  E.,  lecithin,  75 
Girard,  H.,  influence  of  the  nervous 

system  on  fevers,  423 
Gley- 

Antiseptic  properties  of  bile,  86 

Extirpation  of  thyroid,  435 

Reaction  of  intestinal  contents,  152  175 
Goldmann,  E. — 

Cystin,  327,  329 

lodothyrin  in  goiter,  441 
Gorup-Besanez — 

Analysis  of  liquor  pericardii,  226 

Composition  of  bile,  180 
Götschel,  E.  v.,  blood  coagulation,  203 
Gottlieb,    iodothyrin     after     thyroid- 
ectomy, 441 
Gräbner,  F.,  bacterial  poisons,  409 
Graham — 

Colloids,  44 

Decomposition     of     bisulphate     of 
potash,  138 
Grimaux — 

Alantoin,  304 

Colloids,  44,  45 
Grohmann,  W.,  blood  coagulation,  203 
Groth,  O.,  blood  coagulation,  203 
Grube,  K.,  levulose  in  diabetes,  293 
Gruber,  G. — 

Digestion  of  starch,  162,  163 
Grübler,  G.,  proteid  crystals,  48 
Grünewaldt,   O.  v.,  gastric  digestion, 

151 
Gscheidlen,  sulphocyanids,  330 
Gubler,  analysis  of  lymph,  225 
Guerin,  sulphur  in  urine,  326 
Gull,  Sir  Wm.,  thyroid  gland,  430 
Gumlich,  G.,  elimination  of  ammonia 
in  fever,  425 


INDEX   OF   AUTHORS 


461 


Gunning,  anaerobic  life,  244 

Giirber,    albumin  crystals  from  blood 

serum,  53 
Gyergyai,  A.,  peptones,  194,  195 

Habermann,    decomposition    of  Pro- 
teids, 288 
Hadden,  B.,  thyroid  gland,  431 
Hahn,  M.— 

Natural  immunity,  419 

Tubercle  toxin,  415  _ 
Haldane,  carbonic  oxid,  242 
Hale-White— 

Influence  of  the  nervous  system  in 
fever,  423 

Levulose  in  diabetes,  393 
Hall,  absorption  of  iron,  372 
Hallervorden,  ammonia,  292;  in  urine, 

312 ;  its  elimination  in  fevers,  425 
Halliburton,  W.  D  — 

Analysis  of  cerebrospinal  fluid,  227 

Mucin  in  abdomen  after  thyroidec- 
tomy, 436 
Hambui'ger,  H. — 

Absorption  of  iron  salts,  372 

Action  of  gastric  juice  on  pathogenic 
bacteria,  142 
Hammarsten,  O. — 

Analysis  of  bile,   181 ;   of  hydrocele 
fluid,  226 ;  of  milk,  109 

Bile  acids,  177,  178 

Blood  coagulation,  203 

Ferments,  159 

Nuclein  of  milk,  79 

Rennet  ferment,  109 

Salivary  digestion,  129 
Hammerbacher,    excretion    of    oxalic 

acid,  332  n.  4 
Hanau,  A.,  intestinal  juice,  175 
Happel,  functions  of  the  stomach,  148 
Harley,  V.— 

Absorption  of  fat  after  extirpation  of 
pancreas,  166 

Reaction  of  intestinal  contents,  152 
Harnack,  E. — 

Copper  compound  of  egg  albumin,  51 

lodin  drugs,  24,  441 

Lecithins,  76 
Hart,  A.  S.,  composition  of  elastin,  58 
Haubner,  digestion  of  cellulose,  71 
Häusermann,  anemia,  379 
Haycraft,  levulose,  393 
Hayem,  G.j  blood  coagulation,  204 
Hedin,  argmin,  289 
Hedon,  E  — 

Absorption  of  fat  after  extirpation  of 
pancreas,  166 

Pancreatic  diabetes,  398 
Heidenhain — 

Absorption  of  fat,  190 

Lieberkiihn's  glands,  176 

Lymph,  218,  219 

Pancreatic  ferment,  161 

Reconversion  of  peptones,  198 

Secretions  of  gastric  glands,  139 

Secretion  of  HCl  by  glands  of  cardiac 
end  of  stomach,  132 

Sulphur  cyanates,  330 

Urinary  secretion,  317 
Heidenschild,  W. ,  poison  of  rattlesnake, 
418 


Heller,  J.  F.,  chlorin  in  febrile  urine, 

427 
Helman,  M.  C,  tubercle  toxin,  415 
Henneberg,  decomposition  of  cellulose 

in  the  alimentary  canal,  163 
Henninger,  A.,  peptones,  170,  171 
Hen  sen — 

Analysis  of  pathological  lymph,  226 

Glycogen,  343 
Herter,  efiects  of  CO2,  268 
Hermann,  L. — 

Cutaneous  respiration,  273 

Gaseous  exchanges  of  muscle,  252 

Hemoglobinuria,  339 

Nitric  oxid  hemoglobin,  240 

Synthesis  of  proteid,  57 
Heron,  J.,  digestion  of  starch,  163 
Herroun,  E.  F.,  biliary  fistula,  176 
Herth,  R.,  peptones,  167,  170 
Hertwig,  0.,  39 

Heubach,  H.,  excretion  of  alcohol,  117 
Heubner,  O. — 

Iron,  382 

Rennet  ferment,  110 
Heuss,  lactic  acid,  331 
Heyl,  N.,  blood  coagulation,  203 
Hildebrandt,  H  — 

Action  of  enzymes,  417 

lodothyrin  in  goiter,  441 
Hill,  uric  acid,  302 
Hlasiwetz,  decomposition  of  proteids, 

288 
Hobart,  J.,  uric  acid  synthesis,  383 
Hochhaus,  absorption  of  iron,  372 
Hoffman,  A.,  hippuric  acid,  287 
Hoffmann,   Ferd.,  blood    coagulation, 

203 
Hofmann,  A.  W.,  neurin,  401 
Hofmann,  C.  B.,  intestinal  gases,  276 
Hofmann,  F.  A. — 

Diabetes,  388,  402 

Proteid  in  lymph,  228 
Hofmann,  Fr. — 

Absorption  of  proteid,  69 

Cellulose,  73 

Creatin  in  muscle,  128 

Fat  formation,  358,  364 

Glycogen,  343,  365 

Urinary  sediments,  301 
Hofmeister,  Fr. — 

Action  of  pancreatic  ferment  on  gela- 
tins, 166 

Change  in  composition  of  milk,  107 

Crystallization  of  egg  albumin,  52 

Diabetes,  392 

Extirpation  of  thyroid,  434,  435 

lodothyrin  in  goiter,  441 

Peptones,  171,  194-99 

Peptonuria,  199 
Pituitary  body,  446 
Hone,  J.,  bile  acids  in  urine,  336 
Hopkins,  F.  G.— 

Crystallization  of  proteids,  53 

Urobilin,  323 
Hoppe-Seyler — 

Action  of  heat  on  ferments,  160;  of 
bacteria  on  formate  of  lime,  156- 
157 

Anaerobic  fermentation,  158 

Analyses  of  transudations  and  cere- 
brospinal fluid,  225-227 


462 


INDEX    OF    AUTHORS 


Hojjpe-Seyler — continued 

Bile-acids,  178 ;  in  urine,  336 ;  analy- 
sis of,  180-181 ;  composition  of,  180 

Blood  extravasations,  339 

Carbonic  oxid,  240 

Digestion  in  higher  and  lower  ani- 
mals, 152;  of  cellulose,  163 

Gases  in  the  stomach,  143 

Hemoglobin,   215,  239 ;   after  burns, 
275 

Hydration  and  fermentation,  159 

Intestinal  juice,  175 

Lecithin,  75,  77 

Nitric  oxid  hemoglobin,  240 

Oxygen  in  saliva,  246 

Proteid  as  acid,  264 

Eennet  ferment,  109 

Urobilin,  324 ;  in  fevers,  425 
Horbaczewski — 

Creatin,  297 

Digestion  of  elastin,  59 

Uric  acid  in  spleen,  308 
Horsley,    V.,    extirpation    of  thyroid, 

434,  435,  436 
Hoyer,  red  bone  marrow,  231 
Huber,  A.,  ferments,  161 
Hueppe,  F.,  lactic  and  butyric  acids, 

143 
Hüfner,  G  — 

Carbonic  oxid,  240 

Ferments,   action  of  heat  on  dried, 
161 ;  isolation  of,  160 

Hemoglobin,  215,  239 

Isolation  of  pancreatic  ferment,  162 
Huldgren,  E.,  absorption  of  proteid,  69 
Hun,  thyroid  gland,  431 
Hundeshagen,  lecithin,  75 
Hunter,  J.,  self-digestion,  146 
Hiippe,  effect  of  temperature  on  dried 

ferments,  161 
Huschke — 

Lung  surface,  267 

Thyroid  gland,  434 

Hutchinson,  ß.,  active  principle  of 
thyroid  gland,  441 

Iesai,  a. — 
lodothyrin  in  goiter,  441 
Thyroid  administration,  444 

Jacobsen,  bile,  178,  180 

Jacoby,  C,  extirpation  of  suprarenals, 

429 
Jacoby,  M. — 

Extirpation  of  thyroid,  435 

Pituitary  body,  446 
Jaquet,  A. — 

Alcohol,  117-118 

Hemoglobin,  239,  375 

Sulphur  in  proteid,  50 
Jaffe — 

Cystin,  327 

Glycuronic  acid,  260 

Hematoidin,  338 

Indol,  324 

Ornithin,  287 

Urea  in  birds,  309 

Urobilin,  323 
Jaksch,  V. — 

Acetonuria,  391 

Ammoniacal  fermentation,  322 


Jaksch — continued 

Metabolism  in  fever,  425 

Peptonuria,  199 
Jennaret,  decomposition  of  proteid,  288 
Jolyet,  respiration  of  aquatic  animals, 

268 
Jong,  de — 

Diabetes,  392 

Pyrocatechin,  258 
Juvalata,  phthalic  acid,  257 

Kadkin,  p.  R.,  secretion  of  milk,  113 
Kaiser,  removal  of  dog's  stomach,  140 
Karlinski,  typhoid  bacillus  in  urine  and 

feces,  426 
Kast — 
Antiseptic  action  of  gastric  juice,  325 
Sweat,  275 
Keller,  H.,  alcohol,  130;  need  for  salt 

caused  by,  100 
Kellner,  metabolism  during  work,  349 
Kennepohl,  G.,  change  in  the  composi- 
tion of  milk,  107 
Kemmerich — 
Fat  formation,  366 
Meat  extract,  126-127 
Kitasato,  bacterial  poisons,  411, 415,  418 
Kjeldahl,  J.,  diastatic  ferments,  160 
Klees,  R.,  chlorin  in  febrile  urine,  427 
Klemensiewicz,    secretions    of    gastric 

glands,  139 
Klemperer,  G.  and  F.,  action  of  heat  on 

bacteria,  421 
Klikowicz,  alcohol,  121 
Klug,  F.,  respiration  of  frogs,  271 
Knieriem,  v. — 
Amido-acid  in  birds,  309 
Aspartic  acid,  288,  289 
Digestion  of  woody  fibers,  71-72 
Food  value  of  keratin,  58 
Kobert — 
Creatin,  128 
Poison  of  spiders,  416 
Koch,  A.,  ethereal  oils  in  tea,  124 
Koch,  C.  F.  A.,  increase  of  urea  with 

temperature,  424 
Koch,  R  — 
Action  of  heat  on  bacteria,  161,  420 
Comma  bacillus,  142 
Tubercle  toxin,  415 
Kocher,  thyroid  gland,  431,  432-433,439- 

441,  443,  444 
Kochs,  W.,  formation  of  hippuric  acid, 

285 
Köhler,  A.,  blood  coagulation,  205 
Kolbe— 
Taurin,  177 
Uric  acid,  302 
Kölliker — 
Blood  of  splenic  vein,  229 
Functions  of  bile,  183 
König,  J.,  analysis  of  food-stuffs,  65;  of 

milkj  104 
Konjajeff,  typhoid  bacteria  in  kidneys 

and  urine,  426 
Kossel — 
Adenin,  314 
Glycuronic  acid,  260 
Nucleins,  77,  78 
Protamins,  289 
Kotliar,  effect  of  liver  on  poisons,  334 


INDEX    OF    AUTHORS 


463 


Kourlow,  extirpation  of  spleen,  230 
Krsepelin,  E. — , 

Alcohol,  117 

Ethereal  oils  in  tea,  124 
Krasilnikow,  ferments,  159 
Kraus,  Fr.,  metabolism  in  fever,  422 
Kretschy,  F. — 

Alcohol,  121 

Gastric  digestion,  151 
Krüger,  A.,  sulphur  of  proteids,  170, 

327 
Krukenberg — 

Digestion  in  higher  and  lower  ani- 
mals, 152 

Suprarenal  capsules,  430 
Kufferath,  bile  acids,  336 
Kuhn,  Fr.— 

Dilatation  of  the  stomach,  143-144 

Gases  in  the  stomach,  143-144 
Kühne — 

Amido-acids,  167-168 

Attempt  to  isolate  three  pancreatic 
ferments,  161 

Conversion  of  proteid  to  pepton,  167 

Digestion  products,  417 

Hemolysis,  339 

Indol,  324 

Isolation  of  of  ferments,  160 

Pancreatic  juice,  166 

Peptone,  171 

Tubercle  toxin,  415 
Külz— 

Ammonia  in  diabetes,  312 

Cystin,  327 

Diabetes,  386,  391 ;    diabetes  insipi- 
dus, 402,  n.  3 

Glycogen,  343 

Glycogen,  in  diabetes,  396  ;  influence 
of  work  on,  351 

Glycuronic  acid,  260 

Levulose,  387 

Sugar  in  urine,  331 
Kunkel,  A. — 

Bile,  182 

Decomposition  of  cane  sugar,  155 

Gases  of  pancreatic  digestion,  277 

Jaundice,  341 
KuplFer,  oxidation  in  insects,  244 
Kutscheroflf,  cholalic  acid,  177 

Lachowicz,  anaerobism,  244 
Ladenburg,  silicon  compounds,  23 
Lambling — 
Antiseptic  properties  of  bile,  186 
Reaction  of  intestinal  contents,  152, 
175 
Landerer,  A.,  transfusion  of  blood,  205 
Landergren,  E.,  absorption  of  proteid, 

69 
Landwehr,  mucin,  179 
Langbein,  H.,  heat-equivalents  of  food- 
stuffs, 61-62 
Langhaus — 
Changes  in  hemoglobin,  338 
Thyroid  gland,  445 
Langley,  pancreatic  ferment,  161 
Langlois,  P.,  extirpation  of  suprarenal 

capsules,  429 
Lankester,  R.,hemoglobin  ofmuscles,355 
Launelongue,    transplantation  of  thy- 
roid, 442 


Lanz,   0.,   thyroid,  administration  of, 
443,  444;    extirpation  of,   434-438, 
445-446;  subcutaneous  injection  of 
juice  of,  439 
Lapicque,  L.,  need  for  salt,  97 
Laplace,  32 
Laschkewitsch,  274 

Latschenberger,  J.,  absorption  of  pro- 
teid, 192 
Latschinoff,  cholalic  acid,  177 
Laurent,  action  of  alcohol,  122 
Lavoisier — 

Influence  of  muscular  work,  350 

Source  of  animal  heat,  32 
Lea,  Sheridan,  pigments  of  urine,  323 
Leathes,  J.  B.,  mucoid,  179-180 
Lebedefl",  fat  formation,  363 
Lebensbaum,  M.,  51 
Leeds,  oxidation  of  benzol,  250 
Legrain,  action  of  alcohol,  122 
Lehmann,  urinary  calculus,  321 
Lehmann,    C.   G.,    chlorin    in    febrile 

urine,  427 
Lehmann,  F.,  decomposition  of  cellu- 
lose, 163 
Lehmann,   J.,   milk,   analysis  of,  104; 

lime  in,  109 
Lehmann,  K.  B. — 

Food  value  of  gelatin,  57-58 

Intestinal  juice,  173 
Leichtenstein,   administration   oi    thy- 
roid, 443 
Leo,  Hans,  nitrogen,  237 
Lepine,  E. — 

Pancreatic  diabetes,  399 

Sulphur  in  urine,  326 
Lesnik,  glycuronic  acid,  260 
Lesser,  v.,  burns,  275 
Leube,  perspiration,  275 
Ley  den,  E.,  metabolism  in  fever,  422 
Leydig,  intestinal  gases,  276 
Liebermeister,  output  of  CO2  in  fever, 

422 
Liebig — 

Allantoin,  304 

Oxygen  of  blood,  239 

Source  of  muscular  energy,  63,  348 

Sulphur  cyanates,  330 

Urea  of  muscles,  297 

Uric  acid,  302 
Liebreich,  lecithin,  76 
Lilienfeld,    A.,    metabolism    in   fever, 

422,  424 
Lindberger,    antiseptic    properties    of 

bile,  186  _ 
Litten,  acids  in  febrile  urine,  425 
Locke,  F.  S.,  rennet  ferment,  109 
Loew,  O. — 

Isolation  of  ferments,  160 

Nature  of  peptones,  171 

Silver  compounds  of  egg  albumin, 
51-52 
Loewy,  A.,  metabolism  in  fever,  422 
Löfiier,  bacterial  poisons,  411,  414 
Lohrer,  fate  of  ammonia  in  the  body,  291 
Lossnitzer,  attempt  to  isolate  three  pan- 
creatic fei'ments,  161 
Löwit,  M.,  blood  coagulation,  204 
Lubavin,  nuclein  of  milk,  79 
Luca,  de,  saliva  of  Dolium  Galea,  134, 
137 


464 


INDEX    OF    AUTHOES 


Luchsinger — 

Diabetic  puncture,  395 

Glycerin,  362 

Glycogen,  344 
Ludwig — 

Absorption  of  food-stufifs,  187 ;  of  pro- 
teid,  191 

Gases  of  muscle,  350 

Lymph,  218 

Nitrogenous  excretion,  193 

Reducing  substances,  347 

Stomach  in  digestion,  140-141 
Lukjanow — 

Bile,  183 

Effects  of  rarefied  air,  241 
Lunin,  N. — 

Inorganic  salts,  88 

Milk  diet,  72 

Macfadyen— 

Absorption  of  proteid,  192 

Intestinal  contents,   amido-acids   in, 
188 ;  bacteria  in,  143 
Mach,  v.,  hypoxanthin,  309 
Mackenzie,  administration  of  thyroid, 

443 
MacMunn,  suprarenal  capsules,  430 
Magnus,  analysis  of  blood  gases,  243 
Maixner,  E.,  peptonuria,  199 
Mallevre,  A.,  decomposition  of  cellulose 

in  the  alimentary  canal,  163 
Maly— 

Absorption  of  caffein,  123  ;  of  heat  in 
fermentation,  156 

Antiseptic  properties  of  bile,  185 

Bilirubin,  178 

Decomposition  of  proteids,  288 

Diastatic  ferments,  160 

Displacement  of  strong  acids  by  weak, 
136-137 

Isolation  of  ferments,  160 

Peptones,  169-170 

Saliva  of  Dolium  Galea,  134 

Uric  acid,  302 

Urobilin,  323 
Manning,  T.  D.,  intestinal  juice,  173 
Mantegazza,  P. — 

Fibrin,  202 

Granules  in  horse's  plasma,  204 
Maquesne,  inosit,  402,  n.  3 
Maragliano,   diminished    heat    loss    in 

fever,  425 
Marcet — 

Decomposition  of  fats  in  the  stomach, 
164 

Emulsifying  action  of  alkalies,  165 
Marfori — 

Absorption  of  iron,  372 

Oxalic  acid,  332 
Marie,  P.,  pituitary  body,  446 
Marinesco,  G.,  pituitary  body,  446 
Marino-Zucco,  F.  and  S.,  extirpation  of 

suprarenals,  429 
Märker,  digestion  of  starch,  162 
Marshall,  J. — 

Carbonic  oxid,  240 

Hemoglobin,  239 
Marshall,  metabolism  in  fever,  424 
Maschke,  O.,  crystalloids,  46 
Massen,  Eck's  fistula,  296 


Matthia,  N.,  extirpation  of  spleen,  232 
Maydell,  Baron,  94-95 
Mayer,  A.,  artificial  manures,  19 
Mayer,  W.,  softening  of  the  stomach, 

145  n. 
Medicus,  uric  acid,  302 
Meissl,  fat  formation,  367 
Meissner — 

Creatin  and  Creatinin,  125,  297 

Proteid  digestion,  167 

Thiosulphuric  acid,  330 

Uric  acid,   in  birds'   liver,  313[;    in 
birds'  kidney,  318 
Mendel,  administration  of  thyroid,  444; 
effect  of  its  extirpation  on  metab- 
olism, 443 
Mering,  J.  v. — 

Colloid    carbohydrates    in   blood  of 
portal  vein,  163 

Digestion  of  starch,  162 

Duodenal  fistula,  278 

Extirpation  of  pancreas,  398 

Glycogen,  formation,  345 ;  in  diabetes, 
396  ;  hydrolysis  of,  345 

Glycuronic  acid,  260 

Paths  of  absorption,  187,  188 

Phloridzin  diabetes,  346 

Rickets,  85 

Stomach,  acids  of,  144 ;  functions  of, 
148-150 
Merklen,  P.,  transplantation  of  thyroid, 

442 
Mertens,  F.,  extirpation  of  thyroid,  435 
Metchnikoff,  El.,  leucocytes,  223 
Meyer,  A.,  chlorophyll  granules,  39 
Meyer,  G. — 

Absorption  of  proteids,  69 

Breads,  73 
Meyer,  Hans — 

Inorganic  poisons  in  the  blood,  426 

Ornithin,  287 

Phosphorus  oxidation,  255 

Urea  in  birds,  309 
Meyer,  L. — 

Blood  gases,  239 

Carbonic  oxid,  240 

Influence  of  mass,  240 
Michel,  53 
Middleton,  administration  of  thyroid, 

444 
Mieseher — 

Blood  of  splenic  vein  in  fish,  229 

Globulins  of  the  blood  in  starvation,, 
216 

Nucleins,  77-80,  374 

Protamin,  289 

Spleen,  231,  235 
Mill,  oxalic  acid,  332 
Milne-Edwards,    phosphorescence  and 

oxygen,  245 
Minkowski,  O. — 

Diabetic  coma,  404 

Extirpation  of  birds'  kidneys,  309  ;  of 
pancreas,  398 

Fat  absorption,  361 

Jaundice,  340 

Metabolism  in  fever,  425 

Phloridzin  diabetes,  387 

Stomach  contents,  144 

Uric  acid  in  dog,  386 


INDEX   OF    AUTHORS 


465 


Miquel — 

Bacteriainmilk,  110 

HCl  as  antiseptic,  132 
Miura,  alcohol  and  proteid  disintegra- 
tion, 120-121 
Möbius,  excretion  of  bile  pigment,  318 
Moddermann,  oxalate  calculi,  333 
Moers,  lactic  acid  in  urine,  331 
Morgagni,  extirpation  of  spleen,  232 
Molisch,  iron  in  vegetable  life,  22 
Monti,  A.,  milk  diet,  384 
Moore,  B. — 

Absorption  of  fat  after  extirpation  of 
pancreas,  166 

Reaction  of  intestinal  contents,  152 
Moos,  S.,  chlorin  in  febrile  urine,  427 
Moscatelli,  sugar  in  urine,  331 
Mosetig-Moorhoif,  R.  v.,  iodoform  in- 
jections in  goiter,  441 
Mosso — 

Influence  of  the  nervous  system  in 
fever,  423 

Toialbumins,  416 
Moussu,  G.,  extirpation  of  thyroid,  434, 

438 
Mühll,  P.  V.  d.,  alcohol,  117,  118 
Müller — 

Mucin,  179 

Poisonous  effects  of  CO2,  268 
Müller,  Fr.,  functions  of  bile,  183 
Müller,  J. — 

Blood  coagulation,  202 

Ideas  of  space,  2 

Specific  energy  of  the  senses,  9 
Müller,  Max,  fever  temperature,  421 
Müller,  W.,  eflFect  of  low  oxygen  ten- 
sion, 241 
Munk,  I  — 

Alcohol,  121 

Fat  formation,  360 

Lactic  acid,  331 

Sulphocyanic  acid,  330 
Muntz,  saltpeter,  252 
Murisier,  artificial  gastric  digestion,  160 
Musculus — 

Action  of  ferments  on  glycogen,  345 

Ammoniacal  fermentation,  322 

Digestion  of  starch,  162,  163 

Glycuronic  acid,  260 

NÄGELI,  digestion  of  starch,  162 
Napier,  influence  of  thyroidectomy  on 

metabolism,  443 
Nasse,  H.,  analysis  of  lymph,  225 
Nasse,  O. — 

Digestion  of  starch,  162 

Glycogen,  343 
Naunyn,  B. — 

Diabetic  puncture,  395 

Glycogen,   345 ;    its    formation   from 
proteid,  345 

Jaundice,  340 

Nitrogenous  excretions  in  fever,  424 

Urea  excretion  and  temperature,  424 

Uric  acid,  306 
Nencki,  M. — 

Anaerobism,  158,  244 

Bacterial  poisons,  409,  411 

Decomposition  of  fat  by  pancreatic 
ferment,  164;  of  gelatin,  288 

Diabetes,  389 

30 


Nencki — continued 

Hemoglobin,  215 

Hydration  and  fermentation,  159 

Indol,  324 

Intestinal  contents,  168 ;  bacteria  of, 
143 ;  reaction  of,  152 

Lactic  and  butyric  acids,  143 

Oxidation  of  grape  sugar,  248 

Ozone,  250 

Proteid  absorption,  192 
Neubauer — 

Oxalate  of  lime,  333 

Xanthin,  314 
Neumann — 

Extirpation  of  spleen,  231 

Typhoid  bacillus  in  urine,  426 
Neumeister,  R. — 

Albuminuria,  317 

Digestion  products,  417 

Peptones,    formation    from    proteid, 
167  ;  nature  of,  171 
Nicati,  comma  bacillus,  142 
Nieman,  cystinuria,  329 
Nissen,  F.,  secretion  of  milk,  113 
Norwak,  nitrogen  in  respiration,  237 
Nothnagel,  H.,  bacteria  of  lactic  and 

butyric  fermentations,  142 
Notkin,  J.,  active  principle  of  thyroid 

gland,  441 
Nussbaum,  carbonic  acid  tension,  261 

Oeetmann,  salt  frog,  246 
Ogata,  M. — 

Alcohol,  influence  on  digestion,  121 

Stomach,  functions  of,  140-141 
Oliver,  G. ,  suprarenal  capsules,  430 
Oppel,  A.,  absence  of  gastric  digestion 

in  vertebrates,  152 
Osborne,  W.  A.,  invertin,  156 
Ord,  W.  A.— 

Influence  of  thyroidectomy  on  meta- 
bolism, 443 

Myxedema,  430-431 
O'SuUivan,  C,  digestion  of  starch,  162 
Ott,  J.,  influence  of  the  nervous  system 
in  fevers,  423 

Pacanovpski,  H.,  peptonuria,  199 
Pachon,  V.,  partial  extirpation  of  the 

stomach,  140 
Packard,  F.  A.,  pituitary  body,  446 
Pages — 
Blood  coagulation,  205 
Rennet  ferment,  109 
Pal,  J.— 
Extirpation  of  suprarenal   capsules, 

429 
Sugar  in  pancreatic  blood,  401 
Palleske,     administration    of  thyroid, 

443 
Palma,  levulose  in  diabetes,  393 
Panceri,   saliva  of  Dolium  Galea,  134, 

137 
Panum — 
Bacterial  poisons,  413 
Gastric  ulcer,  148 
Vegetable  diet,  71 
Park,   Mungo,  desire  for  salt   among 

negroes,  95 
Parker,  R.,  administration  of  thyroid, 
444 


466 


INDEX    OF   AUTHORS 


Parkes,  alcohol,  120 
Paschutin,  V. — 
Attempt  to  isolate  three  pancreatic 

ferments,  161 
Influence  of  nerves  on  lymph,  318 
Pasteur — 
Anaerobic  fermentation,  158 
Influence  of  heat  on  bacteria,  420 
Paton,  N.— 
Albuminuria,  53 
Biliary  fistula,  176 
Paul,  F.  T.,  pituitary  body,  447 
Pavy — 
Diabetes,  386 

Digestion  of  living  tissue,  146-147 
Pawlow,  J.  P. — 
Eck's  fistula,  296 

Reflex  secretion  of  gastric  juice,  116 
Payen,  digestion  of  starch,  162 
Pean,  excision  of  spleen,  233 
Pellacani,     P.,     suprarenal      capsules, 

430 
Penzoldt,  acids  in  febrile  urine,  425 
Peters,  E..,  rennet  ferment,  110 
Pettenkofer — 
Cutaneous  respiration,  272 
Fat  formation,  359 

Influence  of  work  on  output  of  nitro- 
gen, 350 
Respiratory  apparatus,  270 
Urea  in  diabetes,  388 
Pfeiffer,  analysis  of  human  milk,  104 
Pfeffer,  iron-salts  in  oxidation,  254 
Pflüger — 
Blood,  CO2  of,  264,  265  ;  gases  of,  238 
Fat  formation,  366 
Frog  without  oxygen,  354 
Oxygen,  absorption  by  blood,  243  ;  in 

saliva,  246 
Oxidation  in  salt  frog,  246 
Philipeaux,  extirpation  of  thyroid,  436 
Piccard — 
Nucleins,  77 
Protamins,  289 
Uric  acid,  313 
Pick,  E.  P.,  conversion  of  proteid  to 

peptone,  167 
Pinkus,  S.  N.,  crystallization  of  Pro- 
teids, 53 
Pizzi,  A.,  analysis  of  rabbit's  milk,  104 
Planer — 
Gases  of  intestine,  276 
Sulphuretted  hydrogen,  279 
Plateau,   F.,  digestion  in  higher   and 

lower  animals,  152 
Pliny,  extirpation  of  spleen,  229 
Plosz,  P.,  peptones,  194,  195 
Poehl,  A.,  peptones,  171 
Podolinski — 
Nitric  oxid  hemoglobin,  240 
Origin  of  pancreatic  ferment,  161 
Pohl,  J.,  increase  of  leucocytes  during 

digestion,  197-198 
Pollitzer,  digestion  products,  417 
Ponfick,  burns,  275 
Popoff",  L.,  action  of  lime  on  bacteria, 

156-157 
Pouchet,  extirpation  of  the   spleen  in 

fish,  232 
Prausnitz,  W.,  absorption  of  milk,  69 
Pregl,  Fr.,  intestinal  juice,  173 


Preyer,  W. — 
Blood  gases,  238 
Digestive  glands,  action  in  embryo, 

183 
Oxyhemoglobin,  effect  on  carbonates, 

265 
Preusse,  cystin,  327 
Pribram,    A.,    nitrogen    excretion    in 

fever,  424 
Prior,  nitric  oxid  hemoglobin,  240 
Pröscher,  Fr.,  milk,  analysis  of  dog's, 

104 ;  its  composition  compared  with 

growth  of  suckling,  106 
Proskauer,  bacterial  poisons,  414,  415 
Prudden,  thyroid  gland,  431 

Quincke,  G.— 

Alkalies,  emulsifying  action  of,  165 

Bilirubin,  formation  of,  338 

Intestinal  juice,  172-174 

Iron,  absorption  of,  372 
Quervain,  Fr.  de,  thyroidectomy,  434 

Radziejewski— 
Aspartic  acid,  288 
Indol,  324 

Phosphorescence,  252 
Ranke,  H.,  vegetable  diet,  70 
Ranke  J.,  biliary  fistula,  176 
Rauschenbach,  Fr.,  blood  coagulation, 

203 
Rechenberg,  heat-equivalents  of  food- 
stuffs, 60-62 
Redtenbacher,  chlorin  in  febrile  urine, 

427 
Recklinghausen,  formation  of  bile  pig- 
ment, 338 
Rees — 
Analysis  of  chyle,  225 
Lactic  acid,  331 
Uric  acid,  306 
Regnard,    respiration  of  aquatic   ani- 
mals, 270 
Regnault,  270 

Reichert,  E.  T.,  toxalbumins,  418 
Reihe,  conversion  of  proteid  to  peptone, 

167 
Reinbach,  G.,  thyroid  administration, 

444 
Reinhold,   administration    of  thyroid, 

443   111 
Reiset,  270 ;  nitrogen,  237 
Reverdin,  extirpation  of  thyroid,  431 
Rey-Pailhade,  J.  de,  fermentation,  155 
Ribbert,  pathogenic  bacilli  in  kidneys, 

426 
Richter,  P.,  urea  excretion,  424 
Rieder,  non-nitrogenous  food,  69 
Rietsch,  comma  bacillus,  142 
Ringer,  S.,  metabolism  in  fever,  424 
Ritthausen,  crystalline  proteid,  49 
Robin,  hematoidin^  338 
Robitschek,   J.,  nitrogenous  excretion 

in  fever,  424 
Robson,  M.,  biliary  fistula,  176 
Rockwell,  J. — 

Extirpation  of  thyroid,  435,  437 
Pituitary  body,  446 
Rockwood,  reaction  of  intestinal  con- 
tents, 152 
Roger,  effect  of  liver  on  alkaloids,  334 


INDEX    OF   AUTHORS 


467 


Rogowitsch,  pituitary  body,  446 
Eöhmann,  F.— 

Bile,  functions  of,  183 

Chlorin  in  febrile  urine,  427 
Röhrig,  paths  of  absorption,  187 
Eosbach,  diabetic  coma,  391 
Roussy,  action  of  enzymes,  417 
Roos,  E.,  influence  of  thyroid  on  meta- 
bolism, 439 
Rosenthal,   C,  temperature    in    fever, 

423 
Roux,  bacterial  poisons,  411,  413 
Roxburgh,  R.,  pituitary  body,  447 
Rubner — 

Absorption  of  proteid,  69 

Animal  heat,  34 

Digestion  of  cellulose,  277 

Fat  formation,  368 

Heat-equivalents  of  food-stuffs,  60-62 ; 
regulation,  354 

Vegetable  diet,  70,  71 
Rudel,    absorption    of    calcium    com- 
pounds, 85 
Ruge,  intestinal  gases,  276,  280 

Saae,  M.  C.  du,  rennet  ferment,  109 
Sacharjin,  sodium  in  blood,  208 
Sachs,  conversion  of  fats,  346 

Influence  of  the  nervous  system  in 
fevers,  423 

Silicic  acid  in  plants,  23 
Sachsendahl,  J.,  blood  coagulation,  203 
St.  Martin,  L.,  effects  of  rarefied  air,  241 
Salomon,  urea  formation,  294 
Salkowski,  E. — 

Ammoniaj  fate  of,  291 

Hematoidin,  338 

Hippuric  acid  during  starvation,  282 

Indol,  324 

Oxalic  acid,  257 

Oxidation,  248 

Pepsin,  161 

Taurin,  182 
Sallust,  95 
Salvioli,  G  — 

Peptone  regeneration,  196 

Proteid  in  lymph,  228 

Starvation,  216 
Samson-Himmelstjerna,    J.    v.,    blood 

coagulation,  203 
Saury,  ozone,  248 
Schäfer,  E.  A  — 

Blood  coagulation,  205 

Suprarenal  capsules,  430 
Schaffer,  J. — 

Phenol,  257 

Thymus,  236 
Scharling,  respiratory  exchanges,  350 
Scheremetjewski,      decomposition      of 

sugar,  389 
Scherer,  analysis  of  hydrocele,  226 
Scheube,  uric  acid,  381 
Schiff,  M  — 

Glycogen,  345 

Thyroid,  extirpation,  433,434;  tran- 
plantation,  438 
Schimanski,  nitrogenous  excretion,  424 
Schimraelbusch,  C,  origin  of  thrombi, 

202 
Schlatter,  C,  extirpation  of  stomach, 
142 


Schleich,  effect  of  temperature  on  urea 

excretion,  424 
Schlösing,  saltpeter,  252 
Schmidt,  A. — 

Blood,  CO2  of,  2(^4  ;  coagulation,  203, 
204-205  ;  gases,  237  ;  reducing  sub- 
stances in,  243 

Pepsin,  161 

Rennet  ferment,  109 
Schmidt,  Aug. — 

Alcohol,  excretion  of,  117 

Ferments,  isolation  of,  160 
Schmidt,  C— 

Analyses  of  transudations,  blood 
plasma,  cerebrospinal  fluid,  225-227 

Blood,  analyses  of,  212-215 ;  sodium 
in,  208 

Bile,  functions  of,  183 ;  biliary  fistula, 
176 

Gastric  juice,  130 ;  HCl  in  dog's,  132 

Iron,  absorption  of,  372 

Pancreatic  juice,  Na2COs  in,  165 

Saliva,  secretion  of,  149 ;  amount 
secreted  in  24  hours,  129 

Starvation,  216 
Schmidt-Mülheim — 

Absorption,  paths  of,  187 

Digestion  products,  417 

Intestinal  contents,  amido-acids  in, 
168  ;  reaction  of,  152 

Peptones,  171,  194,  195 

Proteids,  absorption,  191 ;  conversion 
to  peptones,  167 
Schmiedeberg,  O. — 

Alcohol,  117,  118 

Alkaloids  of  fly  fungus,  76 

Bacterial  poisons,  409 

Cartilage,  decomposition  products,  56 

Chondrin,  179 

Crystalloids,  46 

Glycuronic  acid,  259 

Hippuric  acid,  284 

Oxidation,  248 

Proteid,  molecular  weight  of,  47 

Thiosulphuric  acid,  330 
Schnitzler,  pituitary  body,  446 
Schöffer,  A. — 

Carbonic  acid,  261 

Ferments,  isolation  of,  159 
Schönbein — 

Nitrite  of  ammonia,  formation  of,  18 

Ozone,  248 
Schöndorff,    B.,    influence    of  thyroid 

gland  on  metabolism,  439 
Schöndorff,     O.,    iodin    compound    in 

goiter,  440 
Sehönlein,  goiter,  445 
Schotten,  aromatic  amido-acids,  257 
Schoumoff,  C,  on  alcohol,  121 
Schröder,  v. — 

Ammonia  in  birds,  309 

Caffein  as  a  diuretic,  319 

Gastric  digestion,  151 

Hippuric  acid,  256 

Kidneys,  extirpation  of,  293,  309 
Schuchardt,  extirpation  of  stomach,  141 
Schultze,  M.— 

Burns,  effects  of,  275 

Oxidation  in  the  glow-organ,  245 
Schneider,    R.,   absorption  of   caffein, 

123 


468 


INDEX    OF   AUTHORS 


Schultzen,  0. — 
Aromatic  hydrocarbons,  258 
Diabetes,_389 
Lactic  acid,  331 
Leukemia,  307 
Oxalic  acid,  331 
Schulze,  E. — 
Decomposition  of  proteids,  288 
Digestion  of  starch,  162 
Schunek,  oxaluric  acid,  305 
Schütz,  E.,  alcohol,  121 
Schützenberger,  proteid  decomposition, 

288 
Schutzkwer,  absorption  of  caffein^  123 
Schwann,  functions  of  bile,  183 ;  biliary 

fistula,  176 
Schwarz,  L.,  common  salt,  94 
Schwarz,  R.,  extirpation  of  dog's  thy- 
roid, 435 
Schwarzer,   Aug.,  digestion  of  starch, 

162 
Schwendener,  symbionta,  39 
Scriba,  removal  of  dog's  stomach,  140 
Sczelkow — 

Gases  of  blood,  238  ;  of  muscle,  350 
Tension  of  CO,,  261 
Seegen — 
Diabetes,  386 

Fats,  conversion  to  sugar,  346 
Levulose,  387 
Sugar  in  urine,  331 
Seemann,  rickets,  85 
Seifert,  acids  in  febrile  urine,  425 
Selig,  diabetic  puncture,  395 
Selmi,  F.— 
Bacterial  poisons,  409 
Febrile  urine,  426 
Semmer,  G.,  granule  masses,  204 
Senator — 
Albuminuria,  317 

Fever,  metabolism  of,  422 ;  tempera- 
ture of,  423 
Sulphuretted    hydrogen,    effects    of, 

279 
Uric  acid,  386 
Varnishing  skin,  274 
Sendtner,  J.,  action  of  alcohol,  122 
Sertoli,  proteid  as  acid,  264 
Sieber,  N  — 
Grape  sugar,  oxidation  of,  348 
Hemoglobin,  215 
HCl  as  an  antiseptic,  131-132 
Intestinal  contents,  168 ;  bacteria  in, 

143  ;  reaction  of,  152 
Lactic  and  butyric  acids,  143 
Proteid,  absorption  of,  192 
Streptococcus  pyogenes,  415 
Siedamgrotzky,  change  in  the  composi- 
tion of  milk,  107 
Silbermann,   heat-equivalents    of  food- 
stuffs, 61-62 
Silujanoff,  metabolism  in  fever,  422 
Simanowskaja,   E.,   reflex  secretion  of 

gastric  juice,  116 
Simanowski,  N. — 
Alcohol,  121 

Urea,  increase  in  fever,  424 
Simon,  Th.,  lactic  acid  in  trichinosis, 

331 
Simone,  de,  action  of  heat  on  bacteria, 
420 


Slevogt,  F.,  blood  coagulation,  203 
Smith,  A.,  alcohol,  117 
Smith,  E.,  respiratory  exchanges,  350 
Smith,    R.     M.,    absorption    in    dog's 

stomach,  148 
Socin — 

Hematogen,  375 

Levulose  in  diabetes,  393 
Socoloff,  bile  acids,  178 
Söldner,  analysis  of  human  milk,  104 
Sonnenburg,  administration  of  thyroid, 

Soxhlet,  milk,  110 
Spallanzani — 
Antiseptic    action  of    gastric  juice, 

132-133 
Respiration  in  amphibia,  271 
Speck,  C,  respiratory  exchanges,  350 
Spiro— 
Bile,_  182  _ 
Lactic  acid,  355 
Stabel,  H.,  administration  of  thyroid, 

444 
Städeler,  bilirubin,  178 
Stadelmann— 
Ammonia,  312 ;  of  urine,  295 
Bile  pigment,  178 
Diabetes,  391 ;  diabetic  coma,  404 
Jaundice,  339 
Stadthagen— 
Cystin,  327  ;  eystinuria,  329 
Uric  acid  in  spleen,  307 
Xanthin  bases,  314 
Stammreich,  alcohol,  120 
Starling,  lymph,  218 
Steinbach,  ideas  of  space,  2 
Steiner,  J.,  emulsifying ,action  of  alka- 
lies, 165 
Steinhaus,  J.,  secretion  of  milk,  113 
Stern — 
Eck's  fistula,  296 
Liver,  Extirpation  of,  335,  336 
Natural  immunity,  419 
Portal  vein,  ligature  of,  810 
Stieda,  H.,  pituitary  body,  446 
Stilling,  rickets,  85 
Stohmann — 

Cellulose,  decomposition  in  the  ali- 
mentary canal,  163 
Heat-equivalents  of  food-stuffs,  60-62 
Stohr,  Ph.,  leucocytes,  223 
Stolnikow,  Eck's  fistula,  296 
Storch,  phosphorus  poisoning,  363 
Strassburg,  tension  of  CO2,  261,  267 
Strecker,  A. — 
Bile  acids,  177-178 
Creatin,  297 
Lecithin,  75,  76 
Strogonow,  N.,  asphyxial  blood,  241 
Strohmer  fat  formation,  367 
Strümpell,  A. — 
Alconol,  action  of,  122 
Pituitary  body,  447 
Proteid,  absorption  of,  69 
Subbotin,  V— 
Alcohol  excretion,  117 
Fat  formation,  366 
Szabo,  D.,  HCl  in  gastric  juice,  132 
Szydlowski,  L.,  rennet  ferment,  110 
Szymonowicz,  L.,  extirpation  of  supra- 
renals,  429,  430 


INDEX   OF   AUTHORS 


469 


Tacke,  marsh-gas  in  expired  air,  279 
Tamburini,  A.,  pituitary  body,  447 
Tammann,  G.,  fluorin,  24 
Tappeiner^  H. — 

Absorption  in  the  stomach,  148 

Burns,  effect  of,  275 

Cellulose,  decomposition  in  the  ali- 
mentary canal,  163 

Cholalic  acid,  177 

Hippuric  acid,  282 

Intestinal  gases,  276 
Tarchanoflf,  hemoglobin  in  urea,  339 
Tauber,  phenol,  257 
Thanhoffer,  L.  v.,  action  of  bile  on  fat 

absorption,  184 
Thierfelder,  H  — 

Glycuronic  acid,  259 

Hydrolysis  of  jjroteid,  167 
Thiry,  intestinal  juice,  172-174 
Thomsen,      J.,      thermoehemical      re- 
searches, 135-136 
Thudichum,  bilirubin,  178 
Tiagel,  E.— 

Blood-serum  of  snakes,  216 

Fibrin,  202 
Tieghem,  van,  proportion  of  oxygen  to 

light,  31 
Tizzoni — 

Bacterial  poisons,  411,  413,  414 

Extirpation  of  spleen,  230 ;  of  supra- 
renal capsules,  429 

Natural  immunity,  419 
TolmatschelF— 

Cholesterin,  80 

Lecithin  in  milk,  77 
Töpfer,   iodin   in    the    thyroid   gland, 

440 
Traube,  M.,  oxidation,  244,  250 ;   oxy- 
gen-carriers, 253 
Traube,  T.,  temperature  in  fever,  422- 

423 
Trifanowsky,  bile,  acids  of,  178 ;  com- 
position of,  180 
Troschel,  saliva  of  Dolium  Galea,  133- 

134 
Tschervinsky,  N.,  fat  formation,  366 
Tschiriew — 

Nitrogenous  excretion,  193 

Reducing  substances  in  lymph,  246 
Tubby,  H.,  intestinal  juice,  173 

Udranski,   urine,  bile  acids  in,  336; 

sugar  in,  331 
Uffelmann,  J.,  gastric  digestion,  151 
Ughetti,  diet  after  thyroidectomy,  438 
Unruh,   E.,  chlorin    in    febrile  urine, 

427 

Yaillakd— 

Bacterial  poisons,  413,  414,  417 

Leucocytes,  223 
Vas,  B.,  thyroid  administration,  444 
Vassale,  thyroid  administration,  443 
Vauquelin,  allantoin,  304 
Velden,  v.  d.,  aromatic  sulphates,  326 
Vella,  L.,  intestinal  juice,  173 
Vermehren,  administration  of  thyroid, 

443,  444 
Vierordt,  CO2  in  expired  air,  267 

Respiratory  exchanges  during  work, 
350 


Ville,  J.,  absorption  of  fat  after  extir- 
pation of  pancreas,  166 
Vincent — 

Bacterial  poisons,  413,  414,  417 

Leucocytes,  223 
Vinke,  H.  H.,  administration  of  thy- 
roid, 444 
Virchow — 

Gastric  ulcer,  148 

Hematoidin,  338 

Origin  of  thrombi,  202 
Vogel,    A.,    nitrogenous    excretion   in 

fever,  421 
Voit,  C— 

Absorption  of  iron,  372;  ofproteid,  192 

CaiFein  and  nitrogen  output,  124 

Creatin  and  Creatinin,  125,  128,  297 

Fat  formation,  358,  359 

Food  value  of  gelatin,  57-58 

Functions  of  bile,  183 

Glycogen,  345 

Meat  extracts,  126 

Metabolism  during  work,  349 

Nitrogen,    in    respiration,    237 ;    in- 
fluence of  work  on  output  of,  350 

Nitrogenous    equilibrium  in  fasting 
dog,  193 

Starvation,  216 

Sulphur  of  urine,  321 

Urea  in  diabetes,  388 

Urinary  sediments,  301 
Voit,  E.,  rickets,  85 
Voit,  Fr.— 

Absorption  of  calcium  compounds,  85 

Thyroid  administration,  439 
Volhard,  creatin,  297 
Vossius,  jaundice,  341 
Vulpian,  suprarenal  capsule,  430 
Vulpius,  extirpation  of  spleen,  230,  231, 
233,  234 

Wachsmuth,  analysis  of  liquor  peri- 
cardii, 226 
Walter,  Fr.— 
Blood  gases,  238 
Excretion  of  ammonia,  292 
Walter,  G.,  nuclein,  78 
Walther,  Ch.,  transplantation  of  thy- 
roid, 442 
Warrington,  nitrification,  252 
Wassermann — 
Bacterial  poisons,  414,  415 
Febrile  urine,  426 
Weigert,  leucocytes,  223 
Weir  Mitchell,  S.,  toxalbumins,  418 
Weiske,  H. — 
Change  in  the  composition  of  milk, 

107 
Cellulose,  decomposition  in  the  ali- 
mentary canal,  163 
Digestion  of  woody  fiber,  71 
Weiss,  G.,  origin  of  pancreatic  ferment, 

161 
Wendelstadt,  administration  of  thyroid, 

443 
Wenz,  J.,  intestinal  juice,  173 
Werenskiold,  Fr.,  analysis  of  reindeer 

milk,  104,  105 
Wertheim — 
Burns,  275 
Metabolism  of  fever,  422 


470 


INDEX   OF    AUTHORS 


Weyl,  bacterial  poisons,  411 
Wibel,  lactic  acid,  331 
Wiedemann,  glycuronic  acid,  259 
Wieder shi em,  intestinal  epithelium  of 

cold-blooded  animals,  3 
WUliams,  F.,  action  of  inorganic  poi- 
sons on  the  blood,  426 
Wilson,  G.,  fluorin,  24 
Winogradsky,  nitrification,  252 
Winston,  biliary  fistula,  176 
Winternitz,  varnishing  animals,  274 
Wislicenus — 

Ascent  of  Faulhorn,  348 

Lactic  acids,  312 
Wissokowitsch,  lactic  acid,  355 
Wistinghausen,  action  of  bile  on  fat,184 
Wittich,  v.— 

Carmine  excretion,  318 

Diffusibility  of  peptones,  166 

Ferments,  159 
Wöhler — 

Allantoin,  304 

Hippuric  acid,  283 

Uric  acid,  302 
Wolf,  K.,  pituitary  body,  446 
Wolfers,  alcohol,  121 
Wolff",  M.,  effect  of  heat  on  bacteria 

spores,  161 
Wolfi"berg,  tension  of  CO2,  261 
Wolflfhiigel,  eflPect  of  heat  on  bacteria 

spores,  161 
Wolkoff",  A.  v.,  kinetic  energy  and 

intensity  of  light,  30-31 
Wolpe — 

Acetonuria,  391 

Ammonia  in  diabetes,  312 

Butyric  acid,  391 
Woltering,  absorption  of  iron,  372 
Wood,  metabolism  in  fever,  424 
Wooldridge,  L.  C— 

Blood  coagulation,  203,  204 


Wooldridge — continued 

Stromata  of  blood,  206 
Worm-Müller — 

Diabetes,  392 

Oxyhemoglobin  dissociation,  242 
Wörmser,   E.,   extirpation  of  thyroid, 

435,  440,  441 
Woroschiloff— 

Diet  regulation,  70 

Proteid  absorption,  69 
Wrede,  95 
Wroblewski,  analysis  of  human  milk, 

109 
Wurtz,  cholin,  75 

Yeo,  G.  F.,  biliary  fistula,  176 
Yersin,  bacterial  poisons,  411,  413 

Zabelin,  uric  acid,  306 

Zagen,  nitrogen  in  respiration,  237 

Zahn,  F.  W.— 

Blood  coagulation,  203 

Origin  of  thrombi,  202 
Zaleski — 

Carbonic  oxid,  255,  n.  4 

Iron  in  the  liver,  342,  n.  5 

Uric  acid  in  the  kidney,  318 
Zawilski — 

Absorption  of  fat,  190 

Paths  of  absorption,  187 
Zimmerberg,  alcohol,  117,  118 
Zinoffsky,  O.,  hemoglobin  crystals,  50 
Zoja,  52 
Zuntz — 

Alcohol,  121 

CO2  of  blood,  263 

Cellulose,  decomposition  in  the  ali- 
mentary canal,  163 
Zweifel,  embryonic  life,  bile  secretion 
in,  183 ;  oxidation  in,  245 


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qP514                                                     Bob 

~V.-     :.                                                                            1002 

ilv  üiolor;ic    and   ir'atr.olOfric   Cher,  ist r; 

